Atrial natriuretic peptide and bradykinin interaction on norepinephrine uptake in rat adrenal medulla

Interactions between atrial natriuretic peptide (ANP) and bradykinin (BDK) on norepinephrine (NE) uptake were demonstrated in the adrenal medulla of the rat. One hundred nM ANP and 10 nM BDK increased total NE uptake. Subthreshold concentration of ANP (1nM) or BDK (1nM) reverted the effects of thre shold concentrations of both peptides (10 nM BDK and 100 nM ANP respectively). Effective concentrations of ANP and BDK acting simultaneously did not induce additive effects on total NE uptake. Threshold concentrations of both peptides increased neuronal NE uptake only. These results suggest interactions between ANP and BDK at the neuronal uptake level. They confirm that ANP and BDK take part in the regulation of the sympathetic activity in the adrenal medulla of the rat.     

Effect of variations in adrenocortical function on dopamine beta-hydroxylase and norepinephrine in the brain of the rat

The effect of adrenalectomy and corticosterone treatment on dopamine beta-hydroxylase (DBH) activity, catecholamine content and norepinephrine formation and metabolism were studied in the hypothalamus and other parts of the brain of male rats. Two days after adrenalectomy, there was a decrease in DBH activity in the hypothalamus and the brain stem but no change in norepinephrine or dopamine content. Conversion of intraventricularly administered tritiated dopamine to tritiated norepinephrine was slightly increased and norepinephrine was metabolized at a more rapid rate than normal. Corticosterone in a dose of 100 mg/kg increased DBH activity but decreased hypothalamic norepinephrine and copamine content. In adrenalectomized rats, smaller, more physiological doses of corticosterone did not change DBH activity or catecholamine content. The fact that norepinephrine formation and metabolism were increased at the same time that DBH activity in vitro was decreased suggests that DBH is not rate-limiting in adrenergic neurons in the hypothalamus, or that a change in the in vitro activity of the enzyme was not accompanied by a parallel change in its activity in vivo.     

Specificity of amphetamine induced release of norepinephrine and serotonin from rat brain in vitro

Incubation of normal rat cortical or brain stem tissue with 3H-NE or 3H-5-HT and subsequent exposure to amphetamine produced a concentration-related release of the transmitters from tissue stores into the incubation media. Although pretreatment with the catecholamine neurotoxin in 6-hydroxydopamine (6-OHDA) reduced the retention of 3H-NE in both of these tissues, the proportion of 3H-NE released by amphetamine was attenuated only in cortical tissue. Pretreatment with the serotonergic neurotoxin, 5,6-dihydroxytryptamine (5,6-DHT) had no effect on the retention or release of 3H-NE in cortical or brain stem tissue. Pretreatment with 5,6-DHT reduced the retention of 3H-5-HT in the cortex and brain stem, but the release of 3H-5-HT was significantly attenuated only in the latter tissue. 6-OHDA pretreatment increased the retention and proportion of cortical 3H-5-HT released by amphetamine but reduced the release of brain stem 3H-5-HT in the absence of an effect on retention. It appears that the in vitro release of 3H-NE from the cerebral cortex occurs primarily from catecholamine and not serotonergic neurons whereas the cortical release of 3H-5-HT is not an event specific to serotonergic nerve terminals. The release of 3H-5-HT from brain stem does not appear to be restricted to the serotonergic cell bodies since its release was attenuated by 5,6-DHT and 6-OHDA.     

Cinnamate uptake by rat small intestine: transport kinetics and transepithelial transfer

Due to their ubiquitous occurrence in the plant kingdom, plant phenolics, including monomeric cinnamic acids, are ingested by man and animals in variable amounts with their natural diets. Recently, Na(+)-dependent saturable transport of cinnamic acid across the brush-border membrane of rat jejunum has been described. It was the aim of the present study to characterize this mechanism in more detail. We therefore determined the transport kinetics of mucosal uptake of radioactively labelled cinnamic acid under various conditions using a short-term mucosal uptake technique. In addition, the transfer of cinnamic acid across the jejunal wall was investigated using everted intestinal sacs. Investigations of the kinetics of cinnamic acid uptake by the mid-jejunal mucosa revealed the involvement of two transport components, a diffusive Na(+)-independent mechanism and a saturable Na(+)-dependent mechanism. The results obtained with everted sacs provided further evidence of the existence of an active Na+ gradient-driven transport of cinnamic acid across the intestinal epithelium. In the presence of Na+, a significant accumulation of cinnamate occurred inside the serosal compartment and this was strongly inhibited by serosal ouabain. A decrease in the extracellular pH stimulated mucosal cinnamate uptake by increasing the apparent affinity (1/km). This may be attributable to the involvement of a transmembrane H+ gradient in Na(+)-dependent cinnamate transport because the protonophore FCCP caused a significant reduction of cinnamate uptake only in the presence of Na+. The kinetics of cinnamate transport in the absence or presence of a surplus of either unlabelled cinnamate or unlabelled butyrate indicates a reduction in the apparent affinity of the Na(+)-dependent mechanism involved in cinnamate uptake. These results may be explained by a modification of the mechanism by the intracellular pH. Additionally, competitive inhibition of cinnamate uptake by substances structurally related to cinnamic acid may also be involved.     

Oleate uptake kinetics in the perfused rat liver are consistent with pseudofacilitation by albumin

We measured uptake of a representative free fatty acid, oleate, by the single-pass perfused rat liver at oleate:albumin molar ratios of 0.01 to 2:1. For each ratio, uptake was studied at albumin concentrations from 50 to 600 microM. When uptake velocity was plotted as a function of the albumin concentration, the data at each ratio exhibited a pseudosaturation pattern as previously observed in isolated cells (J Clin Invest 84: 1325). At a physiologic albumin concentration of 600 microM, a plot of uptake vs. unbound oleate concentrations was best fitted by the Michaelis-Menten equation (Vmax = 235 +/- 8.8 nmol.min-1.g.liver-1; Km = 130 +/- 12 nM). As the albumin concentration was increased from 50 to 250 microM, the unbound oleate clearance, calculated by either the undistributed sinusoidal or venous equilibrium models, increased progressively, in violation of conventional pharmacokinetic theory, indicating an enhancing effect of albumin on ligand uptake at low albumin concentrations. In contrast, there was no significant difference between measures of unbound clearance at albumin concentrations of 350 and 600 microM. To explain this phenomenon, the clearance data were examined for evidence of facilitation (accelerated dissociation of ligand:albumin complexes) by the clearance ratio test ("square root rule"). All deviations from the predictions of conventional theory were entirely attributable to pseudofacilitation. No data required explanation by a true facilitation model.     

Age-related changes of noradrenergic-NPY interaction in rat brain: norepinephrine, NPY levels and alpha-adrenoceptors

Noradrenergic-neuropeptide Y interaction, which is implicated in different physiological functions, was studied in senescent rats. Norepinephrine (NE) and neuropeptide Y (NPY) levels were measured in brainstem and hypothalamus, and alpha-adrenergic binding was investigated in brainstem in young (4 months) and old (34 months) Wistar rats. NE concentration was the same in senescent rats, whereas NPY concentration was decreased both in brainstem and hypothalamus compared to levels in young rats. [3H]prazosin binding to alpha 1-adrenoceptors was not modified, but [3H]rauwolscine binding to alpha 2-adrenoceptors was altered with age. In fact, the density of alpha 2-adrenoceptors (Bmax) was lower, while the binding affinity (Kd) was increased in old compared to young rats. These results suggest that the decrease of NPY levels could be one of the possible reasons for changes in [3H]rauwolscine binding to alpha 2-adrenoceptors in old rats. The G-protein-adenylate cyclase system, which is impaired in senescent rats, could be involved in the disorganization of noradrenergic-NPY interaction.     

Clenbuterol increases norepinephrine release from rat brain slices by a calcium- and receptor-independent mechanism

Clenbuterol (10-100 microM), a beta 2-adrenergic agonist, potentiated basal (unstimulated) and electrical stimulation-evoked release of 3H-norepinephrine from cerebral cortical slices in a concentration-dependent manner. The beta-adrenergic antagonists propranolol and ICI 118,551 did not antagonize the facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux. Selective down-regulation of beta 2-adrenergic receptors produced by chronic administration of clenbuterol also did not alter this effect of in vitro clenbuterol, despite marked reductions in the density of these receptors. These results suggest that the increase in basal efflux of 3H-norepinephrine observed with clenbuterol was not mediated by beta 2-adrenergic receptors. The facilitatory effect of clenbuterol on basal 3H-norepinephrine efflux was Ca(2+)-independent, which may indicate an amphetamine-like mechanism of action. The enhanced basal efflux of 3H-norepinephrine produced by clenbuterol was stereoselective; there was a four-fold increase in basal 3H-norepinephrine efflux with the (+)-isomer of clenbuterol compared with that induced by the (-)-isomer; this contrasts with the stereoselectivity of the isomers for interacting with beta 2-adrenergic receptors. The present results may explain some of the behavioral actions of clenbuterol, particularly those observed after long-term treatment, and may be relevant to the antidepressant actions of this compound.     

Developmental alterations in N-methyl-D-aspartate stimulated [3H]norepinephrine release in rat brain cortex and hippocampus

Developmental alterations in N-methyl-D-aspartate (NMDA)-stimulated[3H]norepinephrine release from rat brain cortical and hippocampal slices were studied. NMDA (10-1000 microM) resulted in a concentration-dependent increase in [3H]norepinephrine efflux; maximal responses (% released) in the cortex were: (1.53 +/- 0.12, 3.68 +/- 0.20, 2.94 +/- 0.20, 4.60 +/- 0.28 and 5.28 +/- 0.33) and the hippocampal responses were: (1.90 +/- 0.18, 3.84 +/- 0.23, 3.60 +/- 0.28, 5.16 +/- 0.38 and 5.81 +/- 0.45) at varying postnatal ages (1, 7, 14, 21 and 90 days) respectively. Cortical tissue from 7-day-old pups exhibited a transient increase in maximal efflux and a decrease in EC50. These results indicated that developmental alterations in the NMDA receptor appear to be translated into differences in NMDA stimulated [3H]norepinephrine release.     

Changes in mRNA abundance of microtubule-associated proteins in the rat brain following electroconvulsive shock

STUDY DESIGN: Case report and review of the literature. OBJECTIVE: To describe a 72-year-old man with thoracic spinal angiomyolipoma in the ventral aspect of the epidural space and extracanal extension to the posterior mediastinum, to discuss the clinical and radiologic features and unique biologic behavior of this entity, and to review of the literature on angiolipoma and angiomyolipoma. SUMMARY OF BACKGROUND DATA: Spinal angiolipoma and angiomyolipoma are rare tumors, which are localized almost exclusively in the dorsal epidural space of the thoracic spine. Most reported cases have no tendency to involve the surrounding tissue. METHODS: The authors describe the radiologic, surgical, and pathologic findings of this patient and review the findings from other reported cases. RESULTS: Anterior decompression was performed using a right transthoracic incision, and the neurologic symptoms improved immediately. There were no signs of recurrence of the tumor or neurologic deficit within a 2-year follow-up period. CONCLUSION: Results of a literature survey of these tumors support management by prompt and radical surgical intervention for long-term cure, even in cases in which the infiltrating nature is recognized.     

Electroconvulsive shock (ECS) does not facilitate the development of kindling

1. For many years it has been discussed whether repeated electroconvulsive shock (ECS) may induce a lasting epileptogenic effect on the brain (i.e. a kindling effect). In the present study the authors investigated whether weekly ECS do exert such an effect. 2. Bipolar electrodes were implanted in amygdala of 32 rats. Following a two to three week recovery period the rats were randomly allocated to two groups. One group received 12 weekly ECS, the other 12 weekly sham-ECS. 3. Three months after the last ECS/sham-ECS, kindling was initiated. Daily stimulation, eliciting an EEG-afterdischarge was given to all the rats. The animals received a total of 15 stimulations. 4. ECS-pretreated animals did not kindle faster than the sham-group. The two groups reached stage 4 (clonic rearing) after 5.8 (ECS-group) and 5.7 (sham-group) stimulations, respectively. 5. The authors did not find a facilitated development of kindling following ECS, instead they observed a slight, yet statistically significant inhibition of the development of the maximally generalized kindling-seizure--the stage 5 seizure--in the ECS-group. 6. In conclusion: The present study did not show a kindling effect of weekly ECS suggesting that kindling requires more than repeated elicitation of after-discharge.     

Mechanism of valproic acid uptake by isolated rat brain microvessels

In an effort to characterize putative transport systems of valproic acid (VPA) at the blood-brain barrier, the effects of various substrates and inhibitors of known anion transporters on the equilibrium vessel-to-medium concentration (vessel/medium) ratio of VPA were investigated using isolated rat brain microvessels. The equilibrium vessel/medium ratio of VPA was decreased by the presence of high millimolar concentration of unlabeled VPA, indicating that a saturable transport system was involved in VPA transport from medium to microvessels. Short-chain monocarboxylates such as propionic acid, pyruvic acid, and L-lactic acid did not alter the vessel/medium ratio, whereas medium-chain fatty acids and unsaturated metabolites of VPA significantly inhibited the net transport of VPA. Dicarboxylates, tricarboxylate, and p-aminohippuric acid did not affect VPA accumulation in the brain microvessels. Several anionic drugs including salicylic acid, penicillin G, cefazolin, and probenecid significantly reduced the vessel/medium ratio of VPA. In addition, disulfonate inhibitors of inorganic anion exchangers, SH-group modifying reagent, and metabolic inhibitor showed remarkable inhibitory effects on the net transport of VPA between brain microvessels and medium. These results suggest that VPA may be actively transported through the antiluminal membrane via a carrier-mediated system shared by other anionic drugs.     

Electroconvulsive shock does not modify striatal contents of dopamine in MPTP-treated mice

It has been suggested that the therapeutic response to electroconvulsive therapy in depressed patients could be mediated by functional changes in the dopaminergic pathways; a favorable response to electroconvulsive therapy was also observed recently in patients with Parkinson's disease. To study a possible interference of electroconvulsive shock in the course of MPTP-induced parkinsonism in rodents, we measured the striatal content of dopamine in MPTP-treated mice that received electroconvulsive shock at various intervals in the course of MPTP neurotoxicity. Our results showed no immediate or delayed differences in striatal dopamine content of animals that received MPTP and electroconvulsive shock when compared with animals that received only MPTP, thus suggesting that the strong biological effects of MPTP and electroconvulsive shock on the brain may follow different biochemical mechanisms.     

Delivery, distribution, and neuronal uptake of exogenous mannose-terminal glucocerebrosidase in the intact rat brain

OBJECTIVE: To show the utility of ultrasound biomicroscopy (UBM) in imaging small ocular foreign bodies of the anterior segment. DESIGN: Retrospective case series. PARTICIPANTS: Twelve eyes of 12 consecutive patients evaluated in the emergency department or referred to specialty services at 1 institution between August 1994 and November 1997 were examined. INTERVENTION: Ocular ultrasound biomicroscopy was performed. MAIN OUTCOME MEASURES: Detection and localization of an ocular foreign body were measured. RESULTS: An intraocular or superficial foreign body was detected by UBM in 9 (75%) of 12 eyes. The foreign body was classified as corneal in two eyes, subconjunctival in two, intrascleral in three, and intraocular in two eyes. The foreign body was not visible by ophthalmic physical examination in seven of the nine eyes with a confirmed ocular foreign body. In the remaining two eyes, UBM was used to determine the depth of a visible foreign body. In three of the eyes with a confirmed foreign body, computed tomography and/or contact B-scan ultrasonography was obtained and failed to show a foreign body. Six of the foreign bodies were nonmetallic. CONCLUSIONS: Clinical detection of ocular foreign bodies after trauma can be hindered by small size, haziness of the optical media, poor patient cooperation, or hidden location. Ultrasound biomicroscopy is a valuable adjunct in the evaluation of suspected ocular foreign bodies, especially in cases involving small, nonmetallic objects.     

Electroconvulsive shock does not induce c-fos and junB, but TIS1 and TIS8/zif-268, in neonatal rat hippocampus

Insular neurons responsive to baroreceptor challenge have been identified in the rat, but not previously in primates. Characterization of baroreceptor-related neurons was performed in 15 anesthetized monkeys (Macaca fascicularis) using extracellular single-unit recording techniques. 131 units were investigated within the insula and surrounding regions. Based on their responses to phenylephrine hydrochloride (PE) and sodium nitroprusside (SNP), three types of units were distinguished: 35/131 (27%) sympathoexcitatory (SE), 12/131 (9%) sympathoinhibitory (SI) and 84 (64%) null units. More baroreceptive units were found within the insula (38/73, 52%) than in surrounding areas (9/58, 16%) (p < 0.001). Lateralization was indicated with more baroreceptive units being encountered within the right insula (28/44, 64%) than the left (10/29, 34%) (p = 0.02). The majority of the responsive units were located within the dysgranular and granular insula in layers II, III and V/VI. These data suggest that cardiovascular representation may occur in the primate insula as has been shown in other species.