Forearm vascular responsiveness to alpha 1- and alpha 2-adrenoceptor stimulation in patients with congestive heart failure

In the filarial parasite, Setaria digitata, the mitochondria like particles (MLP) show NAD reduction with sodium lactate. The MLP also reduces dye and ferricyanide with lactate. The ferricyanide reduction by lactate is found to be sensitive to the cytochrome o inhibitor orthohydroxy diphenyl (OHD) and complex I inhibitor rotenone, modulated by ADP (+) and ATP (-) and inhibited by pyruvate and oxaloacetate. MLP shows lactate oxidation sensitive to OHD, rotenone and sodium malonate. Thus, the lactate utilizing complex system, consisting of an NADH generating MLP bound lactate dehydrogenase and a lactate flavocytochrome reductase tightly linked to complex I and cytochrome o, produces ATP in functional association with fumarate reductase complex and other enzyme systems. Hence, this study provides new dimensions to the study of metabolism in filarial parasites.     

Increased intracellular potassium and water contents in rat heart after alpha-1-adrenoceptor stimulation

Potassium accumulation in rat heart after alpha-1-adrenoceptor stimulation has previously been reported from indirect measurements. Here we present data on intracellular potassium content measured directly in the heart. Isolated rat hearts perfused in a non-recirculating system were exposed to alpha-1-adrenoceptor stimulation (5 x 10(-5) mol/l phenylephrine in the presence of 10(-6) mol/l timolol). 14C-Sucrose was used to estimate the extracellular space. From heart homogenates intracellular potassium, magnesium and cellular water contents were determined and the ion concentrations calculated accordingly. The intracellular magnesium content remained unchanged during all experimental conditions. alpha-1-Adrenoceptor stimulation evoked an increase in potassium content by 9% (4, 14; 95% confidence interval (CI), P = 0.0006). Due to an observed increase in intracellular water by 17% (9, 26; 95% CI, P = 0.0006), the potassium concentration apparently decreased by 8% (0.3, 15; 95% CI, P = 0.04). During partial inhibition of the Na+/K(+)-ATPase by 10(-5) mol/l ouabain, there was an increase in potassium content by 5% (1, 9; 95% CI, P = 0.008). There was, however, no significant increase in intracellular water in this situation. Calculated intracellular potassium concentration showed accordingly a slight increase. The effects upon potassium and water both in the absence and presence of ouabain were eliminated by the alpha-1-adrenoceptor blocker prazosin (10(-6) mol/l). alpha-1-Adrenoceptor stimulation apparently increased cellular dry weight by 10% (2, 18; 95% CI, P = 0.02). Changes in translocation of potassium and water must be considered as part of the alpha-1-adrenergic heart effects.     

The effects of left ventricular load and contractility on mitral regurgitant orifice size and flow in the dog

Acute mitral regurgitation (MR) was produced in 12 dogs by closed chest partial valvulectomy and the relative contributions of MR pressure gradient (MRG), the time for regurgitant flow (VSI), and the MR orifice area (MRA) to mitral regurgitant volume (MRV) assessed. Aortic and left atrial pressures, biplane left ventricular (LV) angiography, forward flow and mitral regurgitant flow (MRF) were measured following MR induction and following augmentation of left ventricular end-diastolic volume (EDV), increased aortic resistance (angiotensin), and in the presence of increased ventricular contractility (calcium or epinephrine). Mitral regurgitation orifice area was determined by calculation and the diameters of the mitral anulus and subvalvular areas measured angiographically. Angiotensin and volume infusion induced a substantial increase in MRF which was largely dependent on an increase in MRA but not MRG, while augmentation of contractility decreased MRF accompanied by a decrease in MRA, relatively independent of MRG. Left ventricular size and shape are major determinants of MRA and resultant MRF in acute mitral regurgitation. These findings may help to explain the effects of such factors as ventricular loading and volume on the clinical course of mitral regurgitation in man.     

Kinetics of alkylation of cloned rat alpha1-adrenoceptor subtypes by chloroethylclonidine

We quantified and compared the rates at which chloroethylclonidine (CEC) inactivated cloned rat alpha1A, alpha1B-, and alpha1D-adrenoceptors. Membranes from cells transfected with one of the three cloned alpha1-adrenoceptors were incubated for various intervals with 100 microM chloroethylclonidine at 10 degrees C, 25 degrees C or 37 degrees C. The fraction of receptors alkylated by chloroethylclonidine was determined by [3H]prazosin binding. Chloroethylclonidine fully inactivated each alpha1-adrenoceptor subtype via a first order reaction. Alkylation by chloroethylclonidine was markedly slower for the alpha1A-adrenoceptor vs. the other two subtypes (rate constants in 10(-3) min(-1) at 10 degrees C: 0.99 +/- 0.01 (alpha1A), 7.26 +/- 0.15 (alpha1B), and 7.01 +/- 0.12 (alpha1D)). Despite differences in rate, activation energies for alkylation were similar among subtypes. suggesting a similar binding sites for chloroethylclonidine. Computer simulations of kinetic data in mixed receptor populations and experiments with membranes from rat brain showed that nonlinear curve fitting could distinguish relative proportions of alpha1A-adrenoceptor vs. the other two subtypes. We conclude that measurement of the rate of alkylation by chloroethylclonidine, rather than the total amount of alkylation, is most useful in distinguishing the relative proportion of alpha1A-adrenoceptor in tissues.     

Inhibition of alpha1-adrenoceptor-mediated contractions in isolated tail arteries and aorta of the rat by alpha2-adrenoceptor agonists

The effects of alpha2-adrenoceptor agonists, clonidine, tizanidine and UK-14304 on alpha1-adrenoceptor-mediated contractile responses were studied in isolated tail arteries and thoracic aorta of the rat. When applied during sustained contractile responses to almost maximum concentration (10 microM) of phenylephrine, clonidine (0.3 microM to 100 microM) produced concentration-dependent relaxations in both tissues. The maximum relaxation was smaller in tail arteries than in thoracic aorta. Clonidine up to 100 microM failed to relax both tissues precontracted with KCl (60 microM) or U-46619 (1 microM), a thromboxane mimetic. The clonidine-induced relaxation in tail arteries, was reversed by alpha2-adrenoceptor antagonists, yohimbine and idazoxane. Effects of the alpha2-adrenoceptor antagonists were concentration-dependent (0.1 microM to 1 microM), but not in a competitive manner. On the other hand, the relaxation in thoracic aorta was not significantly antagonized by these alpha2-adrenoceptor antagonists. Tizanidine and UK-14304 also relaxed both tail arteries and thoracic aorta precontracted with phenylephrine. The characteristics of the relaxation and their antagonism by yohimbine in both arteries were similar to those induce by clonidine. In tail arteries, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, at a concentration that completely inhibited acetylcholine-induced relaxations did not significantly affect the relaxation induced by clonidine. In contrast, the relaxation of thoracic aorta in response to clonidine was partly reduced in the presence of NG-nitro-L-arginine. These results indicate that the alpha2-adrenoceptor agonists selectively inhibit the contractions induced by phenylephrine in both tissues. Regional differences in the modes of the inhibition by the alpha2-adrenoceptor agonists exist.     

Changes in left ventricular contractility with the phase of respiration

The end-systolic wall stress (sigma(es))-velocity of circumferential fiber shortening (V(cfsc)) relation was defined during the respiratory cycle, in order to obtain a totally noninvasive measure of left ventricular contractility. Eight young, healthy subjects were studied with echocardiography and calibrated carotid pulse tracings, while performing slow paced breathing. Left ventricular sigma(es) vs. V(efsc) relation was determined by fitting linear regression line to data points obtained at different times during the respiratory cycle. Data are given as mean+/-1SD. Left ventricular sigma(es) and V(efsc) exhibited small but significant changes during the respiratory cycle: sigma(es) was highest in late inspiration (56.9+/-4.8 g/cm2) and lowest in late expiration (49.2+/-3.7 g/cm2); inversely, V(cfsc) was lowest during late inspiration (1.18+/-0.17 circ/s) and highest during late expiration (1.34+/-0.20 circ/s). The relation was significant in each subject (r = -0.64+/-0.13) and remained inverse and significant, when it was determined separately for inspiration and expiration (r = -0.61+/-0.17 and -0.68+/-0.12, respectively). At identical end-systolic wall stress, the velocity of shortening was greater during inspiration then expiration, suggesting that contractility was reduced during the expiratory phase. The reduced expiratory contractility might reflect increased vagal influence on the ventricular myocardium.     

Reversal of endothelin-1 release by stimulation of endothelial alpha2-adrenoceptor contributes to cerebral vasorelaxation

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement. DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences. Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen. The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.     

Pharmacological study on functional significance of alpha 1-adrenoceptor subtypes in mammalian ventricular myocardium

The present study was undertaken to determine alpha 1-adrenoceptor subtype involved in the inotropic, electrophysiological and phosphoinositide responses to myocardial alpha 1-adrenoceptor stimulation. Phenylephrine in the presence of the beta-adrenoceptor antagonist, propranolol, elicited a positive inotropic effect in a concentration-dependent manner in both rat and rabbit papillary muscles. In rat papillary muscle, the positive inotropic effect of phenylephrine was antagonized by the alpha 1A-selective antagonist, WB4101, but not affected by the alpha 1B-antagonist, chloroethylclonidine (CEC). On the other hand, the positive inotropic effect in rabbit papillary muscle was antagonized by both WB4101 and CEC. The inotropic response of rat papillary muscle to phenylephrine was composed of a negative inotropic phase and a positive inotropic phase, both of which were blocked only by WB4101. In both rat and rabbit papillary muscles, phenylephrine caused prolongation of action potential duration. WB4101, but not CEC, significantly suppressed the APD prolongation. Only in rat papillary muscle, phenylephrine exerted hyperpolarization of resting membrane potential, an effect which was also eliminated by WB4101. Furthermore, stimulation of phosphoinositide hydrolysis induced by phenylephrine (evaluated by [3H] inositol monophosphate accumulation) was inhibited by WB4101 in a concentration-dependent fashion, but the inhibitory effect on the response to phenylephrine was seen with CEC only at a higher concentration. From these results, it was concluded that both myocardial alpha 1A- and alpha 1B-adrenoceptor subtypes are able to mediate a positive inotropic effect, and that the alpha 1A-adrenoceptor-mediated positive inotropic effect is exclusively dependent on the prolongation of action potential duration, while the alpha 1B-adrenoceptor-mediated one appear to be due to a mechanism other than electrophysiological changes. In addition, based on the previous respects that the phosphatidyl-inositol hydrolytic products do not contribute to the alpha 1-adrenoceptor-mediated electrophysiological effects, the present data suggest that the coupling of alpha 1A-adrenoceptors to phosphatidylinositol hydrolysis may be independent of the positive inotropism.     

Possible mechanism of the negative inotropic effect of alpha1-adrenoceptor agonists in rat isolated left atria after exposure to free radicals

1. This study was designed to investigate the mechanism(s) of the negative inotropic effects of alpha1-adrenoceptor agonists observed in rat isolated left atria after exposure to free radicals. 2. Ouabain and calphostin C were used in contraction experiments to block the sodium pump and protein kinase C. Methoxamine-induced phospholipase C and Na+/K+ ATPase activities were measured. 3. Methoxamine (300 microM) increased contractile force by 1.6 +/- 0.2 mN in control atria but decreased contractile force in electrolysis-treated atria by 2.0 +/- 0.1 mN (P < 0.05), as determined 10 min after methoxamine addition. In contrast, the positive inotropic effects of endothelin-1 (30 nM) and isoprenaline (10 microM) were reduced from 2.6 +/- 0.3 to 1.3 +/- 0.1 mN and from 2.6 +/- 0.3 to 1.7 +/- 0.2 mN, respectively, by electrolysis treatment (P < 0.05), but not converted into a negative inotropic action. 4. In an inositol phosphate assay we observed that the stimulation of phospholipase C by methoxamine was attenuated by electrolysis when the (electrolyzed) medium from the organ bath was used, but the phospholipase C responses were restored by the use of fresh medium. However, fresh medium did not counteract the negative inotropic effect of methoxamine. Accordingly, the negative inotropic effect of methoxamine is not directly related to the impaired phospholipase C responses seen in atria subjected to electrolysis. 5. Ouabain (10 microM) and the protein kinase C inhibitor calphostin C (50 nM), completely prevented the negative inotropic effect of 300 microM methoxamine in electrolysis-treated atria. 6. Measurement of the Na+/K+ ATPase activity, revealed that in control atria, alpha1-adrenoceptor stimulation with 300 microM methoxamine, decreased the Na+/K+ ATPase activity by 14.4 +/- 7.7%. In contrast, methoxamine increased the Na+/K+ ATPase activity by 48.8 +/- 8.9% (P < 0.05) in electrolysis-treated atria. Interestingly, this increase in Na+/K+ ATPase activity was completely counteracted by calphostin C (1.4 +/- 0.1% over basal). 7. These results indicate that the negative inotropic effects of alpha1-adrenoceptor agonists, observed in rat isolated left atria exposed to free radicals, are likely to be caused by protein kinase C-mediated phosphorylation and subsequent activation of the Na+/K+ ATPase.     

Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta

Previous studies showed that alpha-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by alpha 1b- and alpha 1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha 1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 micrograms/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against G alpha q and G alpha o but not G alpha s and G alpha i precipitated specific alpha 1-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G alpha proteins was increased by activating membrane alpha 1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G alpha q and G alpha o, and this response was blocked by the alpha 1-AR antagonist prazosin. Characterization of the alpha 1-AR subtypes that couple to G proteins indicates that although aortic alpha 1a-, alpha 1b-, and alpha 1d-ARs were associated with G alpha q, alpha 1b-AR was also linked to G alpha o. These results suggest that alpha 1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive G(o) protein.     

Antinociception produced by microinjection of morphine in the rat periaqueductal gray is enhanced in the foot, but not the tail, by intrathecal injection of alpha1-adrenoceptor antagonists

Antinociception produced by microinjection of morphine in the ventrolateral periaqueductal gray is mediated in part by alpha2-adrenoceptors in the spinal cord dorsal horn. However, several recent reports demonstrate that microinjection of morphine in the ventrolateral periaqueductal gray inhibits nociceptive responses to noxious heating of the tail by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the feet. More specifically, alpha2-adrenoceptors appear to mediate the antinociception produced by morphine using the tail-flick test, but not that using the foot-withdrawal or hot-plate tests. The present study extended these findings and determined the role of alpha1-adrenoceptors in mediating the antinociceptive effects of morphine microinjected into the ventrolateral periaqueductal gray using both the foot-withdrawal and the tail-flick responses to noxious radiant heating in lightly anesthetized rats. Intrathecal injection of selective antagonists was used to determine whether the antinociceptive effects of morphine were modulated by alpha1-adrenoceptors. Injection of the selective alpha1-adrenoceptor antagonists prazosin or WB4101 potentiated the increase in the foot-withdrawal response latency produced by microinjection of morphine in the ventrolateral periaqueductal gray. In contrast, either prazosin or WB4101 partially reversed the increase in the tail-flick response latency produced by morphine. These results indicate that microinjection of morphine in the ventrolateral periaqueductal gray modulates nociceptive responses to noxious heating of the feet by activating descending neuronal systems that are different from those that inhibit the nociceptive responses to noxious heating of the tail. More specifically, alpha1-adrenoceptors mediate a pro-nociceptive action of morphine using the foot-withdrawal response, but in contrast, alpha1-adrenoceptors appear to mediate part of the antinociceptive effect of morphine determined using the tail-flick test.     

Role of alpha1-adrenoceptor subtypes in production of the positive inotropic effects in mammalian myocardium: implications for the alpha1-adrenoceptor subtype distribution

Both alpha1A- and alpha1B-adrenoceptor subtypes are present in mammalian myocardium. Alpha1-adrenoceptor activation can enhance myocardial contractility, and two possible inotropic mechanisms are proposed: an increase in myofilament Ca2+ sensitivity and an increase in transsarcolemmal Ca2+ influx during action potential prolongation that accompanies the transient outward current inhibition. We suggest that the former is mediated by the alpha1B-adrenoceptor subtype and the latter is by the alpha1A-adrenoceptor subtype. The alpha1B-adrenoceptor subtype may be located on a space more proximal to the sympathetic nerve endings than the alpha1A-adrenoceptor subtype, because the positive inotropic effect of endogenous norepinephrine was mediated entirely by the alpha1B-adrenoceptor subtype. In some species, the sustained positive inotropic effect develops following the transient negative inotropic effect, which is mediated by the alpha1A-adrenoceptor subtype.     

Effects of sumatriptan on coronary flow and left ventricular function in the isolated perfused guinea pig heart

IBD is associated with an increased activation of intestinal immune cells, which causes overproduction of proinflammatory cytokines such as IL-1beta. IL-1beta is implicated in mediating the sustained inflammatory response. IL-1 receptor antagonist (IL-1Ra), the naturally occurring inhibitor of IL-1, has been shown to have beneficial effects in experimental models of colitis. In this study we investigated the hypothesis that an imbalance between IL-1 and IL-1Ra exists in IBD by measuring their secretion by explant cultures of colonic biopsies. Freshly homogenized biopsies from involved tissue in IBD patients exhibited significantly lower IL-1Ra/IL-1beta ratios than control and uninvolved IBD mucosal tissue. Using explant cultures, in vitro production of IL-1beta and IL-1Ra increased progressively during the 4-18-h culture periods. IL-1beta secretion was higher in supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue compared with control tissue, and IL-1beta levels increased with severity of inflammation. IL-1Ra secretion was not elevated in involved IBD samples, but significantly higher levels were released when moderate to severely involved tissue samples were compared with noninflammatory controls. Similar to freshly homogenized tissue, explant studies showed that the IL-1Ra/IL-1beta ratios were significantly decreased in involved IBD tissue, but not in uninvolved CD or inflammatory control specimens. These data support the hypothesis of an imbalance between IL-1beta and IL-1Ra in IBD.     

Alpha1-adrenergic stimulation of sarcolemmal Na+-H+ exchanger activity in rat ventricular myocytes: evidence for selective mediation by the alpha1A-adrenoceptor subtype

Alpha1-adrenoceptor (alpha1-AR) stimulation increases sarcolemmal Na+-H+ exchanger (NHE) activity. The present study was designed to determine the role(s) of alpha1-AR subtype(s) in mediating this response. As an index of NHE activity, acid efflux rates (JHs) were determined in single rat ventricular myocytes loaded with the pH-sensitive fluoroprobe carboxy-seminaphthorhodafluor-1 after 2 consecutive intracellular acid pulses in bicarbonate-free medium. JH at pHi 6.90 did not change significantly during the second pulse relative to the first in control cells but increased in a dose-dependent manner when the second pulse occurred in the presence of phenylephrine (nonselective alpha1-AR agonist) or A61603 (alpha1A-AR-selective agonist), with EC50 values of 1.24 micromol/L and 3.6 nmol/L, respectively (both agonists given together with 1 micromol/L atenolol). Stimulation of NHE activity by 10 micromol/L phenylephrine was inhibited in a dose-dependent manner by the competitive antagonists prazosin, WB4101, and 5-methylurapidil, with IC50 values of 12, 32, and 149 nmol/L, respectively. Analyses of the relative EC50 and IC50 values obtained (and Ki values estimated from the antagonist IC50s) in relation to the relative potencies of these agents at native rat alpha1-AR subtypes and their relative affinities for recombinant rat alpha1-ARs suggest that alpha1-adrenergic stimulation of sarcolemmal NHE activity is likely to be mediated selectively by the alpha1A-AR.     

Preload and incident angle independent index of left ventricular contractility determined by continuous wave Doppler echocardiography

BACKGROUND: Incubating blood with phosphoenolpyruvate decreases hemoglobin oxygen affinity (HOA). This study compared transfusion with phosphoenolpyruvate-treated blood and conventionally stored blood on oxygen consumption in acutely anemic dogs. METHODS: Dogs underwent isovolemic hemodilution (hematocrit = 10%). After 1 hour they were transfused to a hematocrit of 18% with control or phosphoenolpyruvate treated blood. Cardiac output, co-oxymetry, and hemoglobin P50 measurements allowed calculation of oxygen consumption during anemia, and posttransfusion. RESULTS: Hemodilution doubled cardiac output. Transfusion with phosphoenolpyruvate-treated blood allowed greater O2 consumption than control (8.31+/-2.1 and 3.73+/-0.11 cc/kg/mm). There were no differences in arterial or venous PO2 or pH; there were marked differences in HOA, measured by posttransfusion P50 (21+/-3 versus 47+/-4), and mixed venous O2 saturation. CONCLUSIONS: Decreased HOA results in increased O2 consumption in dogs subjected to anemic hypoxia. Phosphoenolpyruvate-treated blood provides increased oxygen consumption at a similar hematocrit when compared with untreated banked blood.     

Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility

The present study examined the performance of rats with neurotoxic lesions centred in the thalamic nucleus medialis dorsalis on standard and modified versions of the eight arm radial maze test. In Experiment 1, the thalamic lesions produced a borderline deficit in acquisition of the standard task, but subsequently had no effect when a delay was interposed after the first four arms had been entered. The same lesions had no effect on T-maze alternation, but they did impair radial-arm maze performance when intramaze and extramaze cues were set against each other. In Experiment 2, lesions of the dorsomedial thalamus impaired acquisition of the standard radial-arm maze task, but combining the results from Experiments 1 and 2 showed that this acquisition deficit was confined to those animals in which bilateral damage extended into the adjacent anterior thalamic nuclei. In addition, lesions of the dorsomedial thalamus disrupted radial-arm maze performance when the task was modified to compare working memory and reference memory and increased activity and exploration. These changes were not associated with anterior thalamic damage. Finally, the thalamic lesions did not affect performance on a test of spontaneous object recognition. It is concluded that lesions of medialis dorsalis do not disrupt spatial memory but do affect other processes that can interact with task performance. These include a failure of extramaze cues to overshadow intramaze cues, a change in activity and exploration levels and deficits in with-holding spatial responses.     

Catecholamine concentrations in rat nasal mucus are modulated by trigeminal stimulation of the nasal cavity

Olfactory mucus provides the perireceptor environment in which the initial steps of olfactory signal transduction occur [5]. Extrinsic autonomic and trigeminal innervation controls mucus secretion and may release neurotransmitters into nasal mucus [13]. We quantitated catecholamines in rat nasal mucus and found that catecholamine levels first increased and then declined with trigeminal stimulation. These data indicate that catecholamine levels are regulated in nasal mucus and could modulate the odor sensitivity of olfactory sensory neurons.