Clinical and immunological criteria of the activity of inflammatory reaction and autolymphokine therapy in penetrating wounds of the eye

Fluorometry of histamine and serotonin in cadaveric blood revealed a threefold increase of their concentrations in comparison with those in whole blood of live subjects. This indicates liberation of amines in the course of death and after it when factors inactivating them cease to function. However, the authors consider it possible to validate their conclusions about changes in the content of histamine and serotonin in cadaveric tissues in different diseases, provided certain conditions of selecting the material are adhered to. The distribution of amines in the viscera is not sex-dependent, little depends on the blood content of tissues, and is determined by the organ-specific features of metabolism of these bioactive substances. To illustrate this, the authors consider the content of histamine and serotonin in the organs of patients dead from hemorrhagic fever with the renal syndrome.     

The effect of the liposomal form of hydrocortisone on the status of cellular and humoral immunity in patients with steroid-dependent bronchial asthma

Skin injury alive produces quick and distinct increase of free histamine and serotonin. A fluorimetric method for detection of these compounds in tissues has been the only one described in the literature up to now but it needed a time consuming extraction and big amount of primary material (about 3 g of skin devoid of subcutaneous fat tissue) as well. The authors succeeded in substituting the method and developed a voltametric detection of histamine and serotonin using the computerized ECO-TRIBO-Polarograph. It enabled to omit the extraction of skin compounds and to decreased the amount of primary tissue to a quarter. The detection of free histamine and serotonin levels is presumed to enable a more accurate determination of the time of injury, particulary in short interval before death; it presents, with a simultaneous of glycophorin, a convenient complementation of immunohistochemical investigation of fibronectin.     

Comparative study of the effects of clozapine and clothiapine in different preparations of guinea pig and rat isolated organs

1. A study has been made to know the effects of clozapine and clothiapine on the responses of rat isolated vas deferens to norepinephrine, dopamine and potassium, those of the rat isolated uterus to serotonin and potassium, and that of guinea pig isolated ileum to histamine. 2. Clozapine was a noncompetitive antagonist to norepinephrine, dopamine, serotonin and histamine; it inhibited potassium-induced contraction in isolated rat uterus and vas deferens. 3. Clothiapine was a competitive antagonist to serotonin and a noncompetitive antagonist to norepinephrine, dopamine and histamine; it inhibited potassium-induced contractions in isolated rat uterus and vas deferens.     

Histamine receptors in the isolated rat stomach fundus and rabbit aortic strips

The effects of histamine and 4-methylhistamine (a selective H2-agonist) were studied on the isolated rat stomach fundus and rabbit aortic strips superfused with Krebs' solution. The contraction induced by histamine was found to be mediated via mepyramine-sensitive H1, while the relaxation induced by the amine through metiamide-sensitive H2-receptors in both smooth muscles. Prior addition of metiamide to the superfusion medium caused an apparent dose-related potentiation in the response to histamine on the aortic strip but not on the stomach fundus strip. The relaxation produced by histamine on the aortic strip demonstrated when the muscle was pretreated with mepyramine and contracted by angiotensin II or serotonin. Metiamide competitively inhibited the relaxation induced by histamine but not by papaverine in both smooth muscles. 4-Methylhistamine produced only a relaxation in the rat stomach fundus which could be competitively inhibited by metiamide. This analog had no agonistic property in the aortic strip. From these results it was concluded that histamine H1-and H2-receptors are present in both smooth muscles. The predominant contractile effect of histamine is mediated through H1-receptors and the relaxing effect of the amine through H2-receptors.     

A study of the vascular and acid-secretory responses of the rat gastric mucosa to histamine

1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2-receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1-receptor antagonists to inhibit the histamine-induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2-receptor agonist, 4-methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti-secretory prostaglandins and H2-receptor antagonists. 7. The selective histamine H1-receptor agonist, 2-pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2-receptors, primarily concerned with acid secretion, and H1-receptors concerned with vasodilatation are both present in the rat gastric mucosa.     

Parental care and intrusiveness as predictors of the abilities-achievement gap in adolescence

High levels of histamine can be found in the airways of asthma patients. This study describes the effects of histamine on anti-CD3-induced production of IL-4, IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and healthy subjects. T cell clones were obtained from bronchoalveolar lavage (BAL) fluid and blood. The number of clones tested, and the percentage of clones in which histamine inhibited or enhanced cytokine production by more than 25%, were as follows: IL-4, 47, 8.5%, and 4.3%; IL-5, 43, 14%, and 30%; and IFN-gamma, 52, 40%, and 15%. Inhibition of IL-5 and IFN-gamma production was reversed by IL-2. The enhancement of IFN-gamma production was associated with an enhancement of both IL-2 production and proliferation. In 21% of the clones a combined effect consisting of inhibition of IFN-gamma production and enhancement of IL-5 production was found. This response was reversed by H2-receptor antagonists and was significantly associated with a histamine-induced increase in intracellular levels of cAMP. The role of cAMP in mediating the histamine effects was supported by the observations that the beta2-agonist salbutamol had effects similar to histamine and that high concentrations of PGE2 mimicked the inhibitory effects of histamine. Clones from BAL fluid and blood showed similar responses, as did clones from patients with asthma and from control subjects. The enhancement of IFN-gamma production by histamine, however, was found only in clones from healthy subjects. The results warrant further investigations on the role of cAMP in the regulation of cytokine production.     

Individual residues contribute to multiple differences in ligand recognition between vesicular monoamine transporters 1 and 2

Molecular cloning has identified two vesicular monoamine transporters (VMATs), one expressed in non-neural cells of the periphery (VMAT1) and the other by multiple monoamine cell populations in the brain (VMAT2). Functional analysis has previously shown that VMAT2 has a higher affinity than VMAT1 for monoamine neurotransmitters as well as the inhibitor tetrabenazine. The analysis of chimeric transporters has also identified two major regions required for the high affinity interactions of VMAT2 with these ligands. We have now used site-directed mutagenesis to identify the individual residues responsible for these differences. Focusing on the region that spans transmembrane domains 9 through 12, we have replaced VMAT2 residues with the corresponding residues from VMAT1. Many residues in this region had no effect on the recognition of these ligands, but substitution of Tyr-434 with Phe and Asp-461 with Asn reduced the affinity for tetrabenazine, histamine, and serotonin. Although the ability to affect recognition of multiple ligands suggests a general structural role for these residues, the mutations did not affect dopamine recognition, indicating a more specific role, possibly in recognition of the ring nitrogen that occurs in tetrabenazine, histamine, and serotonin but not dopamine. The mutation K446Q reduced the affinity of VMAT2 for tetrabenazine and serotonin but not histamine, whereas F464Y reduced serotonin affinity and perhaps histamine recognition but not tetrabenazine sensitivity, providing more evidence for specificity. Interestingly, the Vmax of both VMATs for dopamine exceeded that for serotonin by 3-5-fold, indicating a difference in the speed of packaging of these two neurotransmitters. We also found that VMAT1 has a higher affinity for tryptamine than VMAT2. This mutually exclusive interaction with serotonin and tryptamine also suggests a physiological rationale for the existence of two VMATs. Surprisingly, the residue responsible for this difference, Tyr-434, also accounts for the higher affinity interaction of VMAT2 with tetrabenazine, histamine, and serotonin. Interestingly, replacement of Tyr-434 with alanine increases the affinity of VMAT2 for both serotonin and dopamine and reduces the rate of dopamine transport.     

Blocking effect of tripelennamine on histamine--induced positive chronotropic and inotropic responses of the dog atrium

The effects of histamine on inotropic and chronotropic activity were investigated in isolated canine atrium preparations which were suspended in a bath and perfused with arterial blood from a carotid artery of heparinized support dog. Histamine administered into the cannulated sinus node artery in a dose range of 0.3-100 mug produced dose-related positive chronotropic and inotropic effects. The positive responses to histamine were not suppressed by treatment with propranolol in doses which blocked responses to norepinephrine, but these were significantly suppressed by a histamine H1 receptor blocking agent, tripelennamine. On the other hand, these histamine-induced effects were not modified by a histamine H2 receptor blocking agent, burimamide. From these results, it is assumed that positive chronotropic and inotropic effect of histamine may be mediated by histamine H1 receptors in the dog heart.     

Transient increase of blood histamine level induced by pentagastrin. Continuous monitoring by in vivo microdialysis

BACKGROUND: Since few studies of (penta)gastrin-induced histamine release from the gastric mucosa into blood has been performed, an effect of pentagastrin on histamine level of rat blood was examined by using the in vivo microdialysis method. METHODS: Pentagastrin was perfused through the microdialysis probe implanted into the jugular vein of urethane-anesthetized rats or in urethane-anesthetized, totally gastrectomized rats, and dialysis samples of blood were concurrently collected. Histidine decarboxylase (HDC) activities and histamine contents in the glandular stomach and gastric acid output after pentagastrin stimulation were also investigated. RESULTS: Pentagastrin induced a transient increase of blood histamine in a dose-dependent manner but failed to cause any increase of blood histamine in the totally gastrectomized rat. Pentagastrin also induced increases of the HDC activity in the glandular stomach and of the gastric acid output. The peak histamine level in blood occurred 40 min after pentagastrin perfusion, whereas the peak acid secretion occurred after 80-120 min and then leveled off. CONCLUSIONS: The transient increase of blood histamine induced by pentagastrin is attributable to the histamine released from enterochromaffin-like cells and could be monitored by using the in vivo microdialysis method.     

Hemorrhage during the third stage of labor and the postpartum period

Differentiation between pollinosis and vasomotor rhinitis creates great diagnostic difficulties. The aim of this study was to conduct comparative immunological clinical studies contrasting these two distinct diseases. Thirty-one subjects with untreated pollinosis and 29 subjects with untreated symptoms of rhinitis were tested, determining their T and B lymphocyte counts and the counts of their subpopulations, the levels of immunoglobulin A, M, G, D and E, both separately and in total, and levels of both basal and whole histamine. The control group was comprised of 30 healthy subjects. The results of this study show that these two diseases differ from each other (p < 0.05) in the recorded levels of basal histamine, total IgE, and IgG, IgM and IgD, as well as the count of T-RFC lymphocytes, T lymphocytes with receptors for Fc IgG and B lymphocytes with superficial receptors for IgG. The most useful laboratory methods for diagnosing the difference between pollinosis and vasomotor rhinitis appear to be the determination of levels of basal histamine and IgD in the blood.     

Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo

Catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL), reduces catecholamine secretion from chromaffin cells in vitro. We investigated the effects of this peptide on catecholamine release and blood pressure in vivo. Intravenous catestatin reduced pressor responses to activation of sympathetic outflow by electrical stimulation in rats, and the catestatin effect persisted even after adrenergic (alpha plus beta) blockade. Catestatin did not alter plasma norepinephrine levels, but increased plasma epinephrine 11-fold. Catestatin also blunted pressor responses to exogenous neuropeptide Y agonists. A control peptide (chromogranin A(141-160)) did not alter pressor or catecholamine responses to electrical stimulation. Pretreatment with a histamine H1 receptor antagonist blocked both the vasodepressor response to catestatin and the elevation in plasma epinephrine. Catestatin elevated endogenous circulating histamine 21-fold, and exogenous histamine mimicked both the epinephrine elevation and the vasodepressor actions of catestatin. We conclude that catestatin is a potent vasodilator in vivo whose actions appear to be mediated, at least in part, by histamine release and action at H1 receptors.     

Detection and quantification of Epstein-Barr virus EBER1 in EBV-infected cells by fluorescent in situ hybridization and flow cytometry

BACKGROUND: The level of histamine in nasal lavage fluid has been used as an index of mast cell/basophil activation in a number of studies. Obviously, such an index can only be valid if changes in the secretory activity of nasal glands do not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a simultaneous activation of mast cells/basophils in the nasal mucosa, must not increase the level of histamine). OBJECTIVES: To asses the effect of nasal hypersecretion on histamine levels in lavage fluid. METHODS: Nasal challenges were performed with methacholine and allergen in grass pollen-allergic patients and non-allergic controls. Nasal lavage fluid was collected before and repeatedly for nine hours after nasal challenge, and the level of histamine was compared with that of a specific mast cell-derived enzyme, tryptase. In addition, the effect of methacholine on basophils was examined in vitro. RESULTS: Allergen challenge of allergic patients produced sneezing and a significant increase in histamine and tryptase levels, whereas challenge of non-allergic subjects produced no such response. Interestingly, challenge with methacholine also induced a significant increase in histamine levels. This increase was seen in both allergic and non-allergic subjects and it was not associated with any sneezing or increase in tryptase levels, indicating that mast cells were not activated. Furthermore, stimulation of basophils with methacholine did not induce any histamine release in vitro. CONCLUSIONS: Apparently, there exists a pool of histamine in the human nose that can be transferred to lavage fluid during glandular hypersecretion. The source of this histamine is yet to be identified. As the level of histamine seems to be affected by the secretory activity of nasal glands, we question the use of this single mediator as an index of mast cell/basophil activation in nasal lavage studies.     

Multiple residues contribute independently to differences in ligand recognition between vesicular monoamine transporters 1 and 2

The two closely related vesicular monoamine transporters (VMATs) 1 and 2 differ substantially in ligand recognition. The neuronal VMAT2 exhibits a higher affinity for monoamine substrates and in particular for histamine as well as a greater sensitivity to the inhibitor tetrabenazine than the nonneuronal VMAT1. The analysis of chimeric transport proteins has previously shown that two major domains, one spanning transmembrane domains (TMDs) 5-8 (TMD5-8) and the other, TMDs 9-12 (TMD9-12), are required for the high affinity interactions characteristic of VMAT2. Using site-directed mutagenesis to replace residues in TMD5-8 of VMAT2 with the equivalent residues from VMAT1, we now show that the sensitivity of VMAT2 to tetrabenazine requires Ala-315, and this interaction occurs independently of the interaction with residues in TMD9-12. The ability to recognize histamine as a substrate depends on Pro-237, and the contribution of TMD9-12 to histamine recognition appears to involve a common mechanism. In contrast, the replacement of many residues in TMD5-8 of VMAT2 with equivalent residues from VMAT1 improves the recognition of both serotonin and tryptamine, and these mutations show a dominant effect on the recognition of both tryptamine and serotonin over mutations in TMD9-12. The results indicate that different ligands interact through distinct mechanisms with the VMATs and that the recognition of each ligand involves multiple, independent interactions with the transport protein.     

Monoamine- and histamine-synthesizing enzymes and neurotransmitters within neurons of adult human cardiac ganglia

BACKGROUND: Cardiac ganglia were originally thought to contain only cholinergic neurons relaying parasympathetic information from preganglionic brain stem neurons to the heart. Accumulating evidence, however, suggests that cardiac ganglia contain a heterogeneous population of neurons that synthesize or respond to several different neurotransmitters and neuropeptides. Reports regarding monoamine and histamine synthesis and neurotransmission within cardiac ganglia, however, present conflicting information or are limited in number. Furthermore, very few studies have examined the neurochemistry of adult human cardiac ganglia. The purpose of this study was, therefore, to determine whether monoamine- and histamine-synthesizing enzymes and neurotransmitters exist within neurons of adult human cardiac ganglia. METHODS AND RESULTS: Human heart tissue containing cardiac ganglia was obtained during autopsies of patients without cardiovascular pathology. Avidin-biotin complex immunohistochemistry was used to demonstrate tyrosine hydroxylase, L-dopa decarboxylase, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, tryptophan hydroxylase, and histidine decarboxylase immunoreactivity within neurons of cardiac ganglia. Dopamine, norepinephrine, serotonin, and histamine immunoreactivity was also found in ganglionic neurons. Omission or preadsorption of primary antibodies from the antisera and subsequent incubation with cardiac ganglia abolished specific staining in all cases examined. CONCLUSIONS: Our results suggest that neurons within cardiac ganglia contain enzymes involved in the synthesis of monoamines and histamine and that they contain dopamine, norepinephrine, serotonin, and histamine immunoreactivity. Our findings suggest a putative role for monoamine and histamine neurotransmission within adult human cardiac ganglia. Additional, functional evidence will be necessary to evaluate what the physiological role of monoamines and histamine may be in neural control of the adult human heart.     

Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin

In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m2 of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m2. No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m2 dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists an analogous UVA-induced pruritus in human skin.     

Endothelial dysfunction in cerebral vessels following carotid artery infusion of phorbol ester in rabbits: the role of polymorphonuclear leukocytes

The effect of 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) on endothelium-dependent and endothelium-independent vasoconstriction and vasodilation was studied in isolated segments of rabbit middle cerebral artery (MCA). Concentration-dependent responses of the left and right MCA to the constrictors KCl, noradrenaline, uridine 5'-triphosphate, serotonin, and histamine, as well as to the dilators acetylcholine, bradykinin, sodium nitroprusside, and calcium ionophore (A23187), were compared in control animals and after PMA injection into the left common carotid artery. In the control animals there was no significant difference in the responses of the left and right MCA to either the constrictors or the dilators studied. After PMA injection the endothelium-dependent relaxation in response to acetylcholine, bradykinin, and A23187 was reduced in the left MCA (PMA-injected side), whereas the effect of the endothelium-independent dilator sodium nitroprusside remained unchanged. Simultaneously greater contractile responses of the left MCA to serotonin and histamine were obtained. Neither infusion of L-arginine in vivo before the PMA injection nor incubation of the isolated MCA segments with L-arginine affected this difference in MCA reactivity. Platelet depletion did not change the PMA-induced reduction in the endothelium-dependent relaxation, whereas after leukocyte depletion this reduction practically disappeared. These results suggest that the PMA-induced brain microembolia causes acute endothelial dysfunction, which is possibly mediated by intravascular activation of leukocytes and is independent of nitric oxide synthesis from L-arginine. This phenomenon might play an important role in cerebral angiospastic disorders after intravascular activation of leukocytes in cerebral ischemia and reperfusion.     

Controversial association of left ventricular hypertrophy and the ACE I/D polymorphism--is the mist clearing up?

The calcium channel blocker nifedipine has analgesic properties that are enhanced by nicotine. Although it is not known how this analgesic state might affect the awareness of anginal pain and impending myocardial infraction, recent studies have shown an increased mortality associated with the use of large doses of nifedipine. Because both nifedipine- and nicotine-induced analgesia involve serotonergic mechanisms, we studied the effects of the serotonin biosynthesis inhibitor parachlorophenylalanine (pCPA) on nifedipine- and nicotine-induced analgesia. Nociception was assessed by tail-flick method. Rats pretreated with pCPA (300 mg/kg intraperitoneally [IP]) followed by either nifedipine (15 mg/kg IP) or nicotine (1 mg/kg subcutaneously) had a increase in tail-flick latency of 41% (P = 0.09) and 50% (P = 0.05), respectively, compared with animals that did not receive pCPA. Additionally, rats pretreated with pCPA followed by a combination of nicotine and nifedipine doubled their tail-flick latency (P = 0.0001) compared with animals that were not treated with pCPA. These data further support the involvement of the serotonergic system in both nifedipine- and nicotine-induced analgesia and suggest that drugs that affect serotonin levels, including tricyclic antidepressants and serotonin-specific reuptake inhibitors, may also affect the analgesia induced by nifedipine and nicotine. IMPLICATIONS: This study examines the effect of serotonin depletion on nicotine- and nifedipine-induced analgesia. Nifidipine is a calcium channel blocker used to treat high blood pressure. It also has pain-relieving properties that are enhanced by nicotine. Because both nifedipine- and nicotine-induced analgesia involve the neurotransmitter serotonin, it is important to know how changes in serotonin concentration might affect both nicotine- and nifedipine-induced analgesia. This study not only supports the involvement of the serotonergic system in both nifidipine- and nicotine-induced analgesia, but also suggests that drugs that affect serotonin levels may also affect analgesia induced by nifidipine and nicotine.     

Serotonin concentration in the blood of patients with hemorrhagic fever with renal syndrome

Differences in the concentrations of serotonin in whole blood and plasma of patients with hemorrhagic fever with the renal syndrome prompted measurements of serotonin in different components of the blood. The concentration of serotonin in whole blood was found to depend on its hemoconcentration: the higher is the hematocrit, the greater is the difference between serotonin content in the plasma and whole blood. In case of hemoconcentration or hemodilution it is impossible to assess serotoninemia from the level of serotonin in whole blood.     

Angiotensin II inhibits glomerular adenylate cyclase via the angiotensin II receptor subtype 1 (AT1)

We examined the role of angiotensin II (AII) receptor subtypes in the regulation of hormone-stimulated cyclic AMP (cAMP) accumulation in isolated rat glomeruli. All inhibited cAMP formation induced by histamine, serotonin and parathyroid hormone, but not by prostaglandin E2 or calcitonin gene-related peptide. Angiotensin III but not the angiotensin fragments (1-7) and (3-8) also showed inhibitory activity. The inhibition of histamine-induced cAMP accumulation by AII was concentration-dependent and was absent in glomeruli isolated from pertussis toxin-treated rats. The effect of AII on histamine-induced cAMP levels was not mimicked by the protein kinase C activator, phorbol-12-myristate-13-acetate, nor was the effect of AII inhibited by the protein kinase C inhibitors, staurosporine and H-7. The angiotensin II receptor subtype 1 (AT1) antagonists, SK&F 108566 and losartan, attenuated the inhibitory effect of AII on histamine-stimulated cAMP accumulation, whereas the AT2 selective antagonists, CGP 42112A, WL-19 and PD 123319, had no effect. Displacement of [125I]AII from glomerular membrane using the subtype-selective antagonists confirmed that the glomerular AII receptor has characteristics of an AT1 subtype. The results suggest that AII, through activation of the AT1 receptor, may act to maintain the contractile state of glomerular mesangial cells by attenuating the increase in cAMP levels induced by some hormones.     

Multivariate analysis (''forensiometrics'')--a new tool in forensic medicine. Differentiation between sharp force homicide and suicide

Previous studies have shown that corticosteroids affect the changes in membrane potential evoked in CA1 hippocampal neurons by serotonin and the metabolically stable cholinergic analogue carbachol: Low corticosteroid levels induced by steroid administration to adrenalectomized rats or obtained in adrenally intact rats were associated with small transmitter responses. High corticosteroid levels induced by exogenous corticosteroid application or by an acute stress in adrenally intact rats generally evoked large transmitter responses. In the present study we investigated the consequences of this steroid modulation for the main stream of synaptic information in the CA1 hippocampal region, which is carried by amino acids. To this purpose the effect of serotonin and carbachol administration on both extracellularly and intracellularly recorded synaptic responses to Schaffer collateral stimulation were investigated. The data show that the effect of in vivo activation of corticosteroid receptors on the serotonin-induced hyperpolarization of the membrane responses is clearly reflected in the inhibitory effect of serotonin on synaptic responsiveness in the CA1 area. Low circulating levels of corticosterone or selective mineralocorticoid receptor activation reduced the serotonin mediated inhibition of synaptically evoked responses, whereas high corticosterone levels were associated with strong serotonin mediated suppression of synaptic responses. This steroid modulation seems to be specifically aimed at serotonin neurotransmission, as the cholinergic effects on excitatory synaptic transmission were not affected by the hormone treatment.