摘要:

Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H1) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 μg/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2–10 μg/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 μg/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 μg/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with Hi resulted in the significant inhibition of H1-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after Hi injection at a dose of 5 μg/kg. Intravenous infusion of hexamethonium continued before and after Hi injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by Hi. From these findings, it can be concluded that intracerebroventricular injection of Hi caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by Hi is certainly produced without participation o

ISSN:0031-7012    

DOI:10.1159/000139081

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Many reports indicate that nonsteroidal anti-inflammatory drugs exert their antinociceptive effect through adrenergic and serotoninergic systems. We investigated the acute and chronic effects of phenazone on the pain threshold and on brain serotonin binding sites. A relationship between phenazone serum levels and the antinociceptive effect was found; acute treatment with phenazone provokes a significant decrease in serotonin binding sites both in the pons and cerebral cortex after 2, 4 and 8 h, but not after 24 h. After 15 and 30 days of treatment, the number of binding sites increases both in the pons and cortex.

ISSN:0031-7012    

DOI:10.1159/000139082

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effects of intravenous administration of melatonin (30–60 mg/kg) or vehicle (10% alcohol) on arterial pressure, heart rate, blood gases or brain serotonin release were assessed in rats under urethane anesthesia. Administration of melatonin, but not the vehicle, produced a dose-related fall in mean arterial pressure, heart rate, or serotonin release in both the corpus striatum and the hypothalamus. Melatonin treatment had an insignificant effect on either PaCO2, PaO2 or pH. In addition, the melatonin-induced depressor responses were abolished by pretreatment with spinal transection, whereas melatonin-induced bradycardia was abolished by pretreatment with bilateral vagotomy. These results suggest that melatonin decreases brain serotonin release and results in sympathetic inhibition or parasympathetic stimulation which leads to hypotension and bradycardia in rat

ISSN:0031-7012    

DOI:10.1159/000139083

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The purpose of this study was to investigate the effects of 9-amino-1,2,3,4-tetrahydroacridine (THA; Tacrine®) on muscarinic-receptor-linked second-messenger systems in rat brain and to determine the selectivity and mechanisms of these effects. Both competitive and noncompetitive antagonism was revealed in saturation radioligand binding studies performed in cortical and striatal tissue, depending on THA concentration. Micromolar THA concentrations blocked muscarinic-receptor-mediated inhibition of cAMP formation and stimulation of phosphoinositide (PI) hydrolysis with poor selectivity between the two responses. While both responses were blocked in the same concentration range (4–60 µmol/l), non-competitive antagonism of PI hydrolysis occurred at THA concentrations greater than 10 µmol/l while competitive antagonism was displayed for the cAMP response at concentrations of THA up to 40 µmol/l. THA was equally effective at inhibiting PI hydrolysis stimulated by histamine, phenyleph-rine or oxotremorine-M, when these agonists were employed in concentrations equal to their EC50s for the response. THA did not antagonize PI hydrolysis mediated by the quisqualate receptor at any agonist concentration used. Furthermore, THA blocked carbachol- but not morphine-induced inhibition of forskolin-stimulated cAMP formation in the str

ISSN:0031-7012    

DOI:10.1159/000139084

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In superfused pig retina discs, preincubated with 3H-nor-adrenaline, the electrically (3 Hz) evoked tritium overflow was inhibited by γ-aminobutyric acid (GABA) and the GABAB receptor agonist R-(–)-baclofen but was not affected by the GABAA receptor agonist 3-amino-1-propanesulphonic acid. The effect of GABA was counteracted by the GABAB receptor antagonist CGP 35348 [P-(3-aminopropyl)-P-diethoxyme-thylphosphinic acid] but was not influenced by the GABAA receptor antagonist SR 95531 [2-(3-carboxypropyl)-3-amino-6-paramethoxyphenylpyridazinium bromide]. Furthermore, CGP 35348 antagonized the inhibitory effect of R-(–)-baclofen on the electrically (0.66 Hz) evoked tritium overflow in superfused rat vena cava segments, preincubated with 3H-noradrenaline, and on the electrically (0.5 Hz) induced rise in diastolic blood pressure in pithed rats. The present results suggest that GABA is capable of inhibiting noradrenaline release (most likely from vascular sympathetic nerve endings) in the pig retina via GABAB receptors and that CGP 35348 is a valuable tool for the characterization of GABAB receptors in vitro and in

ISSN:0031-7012    

DOI:10.1159/000139085

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Following preloading of striatal synaptosomes with 3H-dopamine (DA), the kinetics of release have been followed for a 60-min incubation period. DA appears to be totally releasable under both depolarizing (veratridine) and nondepolarizing conditions. Cocaine has no significant effect on release under either condition. Release is consistent with a model consisting of two parallel, linear compartments (when plotted as a log function). It is proposed that the slower compartment might represent the operation of the DA transporter, while the faster compartment might represent vesicular release.

ISSN:0031-7012    

DOI:10.1159/000139086

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Potential alteration of ouabain-induced cardiotoxicity by γ-aminobutyric acid (GABA) in rats was tested by infusing ouabain for 10 min (0.7 mg/kg/min, i.v.) before or after continuous infusion of Ringer’s solution with or without GABA (1 mg/min, i.v.). GABA evoked hypotension and bradycardia of similar magnitude under both conditions. The incidence of ouabain-induced ventricular fibrillation (VF) or cardiac arrest (CA) was similar in both groups. However, the time intervals to onset of VF and CA, in rats given ouabain before, but not after, GABA were shorter than in rats treated with Ringer’s solution (p < 0.05). In experiments where baclofen (0.034 mg/min, i.v.) was infused after ouabain, hypotension and bradycardia occurred, but the incidence and times of ouabain-induced VF and CA were similar to control values. These results suggest that the enhancement in ouabain cardiotoxicity was mediated by GABAa recep

ISSN:0031-7012    

DOI:10.1159/000139087

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The present study was designed to examine the reaction pathway of colloidal bismuth subcitrate (CBS) with thiols. Studies were performed using the monothiol glutathione (GSH), the dithiol dithiothreitol (DTT) and the thiol enzymes papain and H+/K+-ATPase. UV-vis spectra showed that CBS forms complexes with GSH and DTT. The GSH/CBS complex but not the DTT/CBS complex was cleared by 5,5’-dithiobis-(2-nitrobenzoic acid). CBS inhibited H+/K+-ATPase (IC50: 23 ± 6.5 µmol/l) but failed to inhibit papain activity. The inhibitory action of CBS on H+/K+-ATPase-mediated proton transport was prevented by the dithiol dithioerythritol but not by GSH. These results indicate that CBS forms stable complexes with dithiols and instable complexes with monothiols. We suggest that some of the effects of CBS (i.e., stimulation of prostaglandin production, antibacterial action against Helicobacter pylori) are mediated via the blockade of SH-gro

ISSN:0031-7012    

DOI:10.1159/000139088

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The effects of colloidal bismuth subcitrate (CBS) on porcine pepsin have been studied in vitro. CBS inhibited pepsin activity in a pH-dependent manner. CBS was not active at pH 4.0 but inhibited pepsin activity at pH 1.0 (IC50: 2.3 ± 0.09 mmol/l) and pH 2.0 (IC50: 8.9 ± 0.7 mmol/l). This inhibition was reversible. In the presence of the sulfhydryl ligand mercaptoethanol, which prevents precipitation of CBS, the inhibitory potency of CBS increased. CBS bound to both positively (Amberlite) and negatively charged (Dowex) ion exchangers in a pH-dependent manner. With increasing acidity, binding to Amberlite increased, whereas binding to Dowex decreased. From these data we conclude that negatively charged bismuth salts derived from CBS bind at pH 2.0 and 1.0 via an ionic interaction to positively charged groups of pepsin, thereby inactivating the enzym

ISSN:0031-7012    

DOI:10.1159/000139089

出版商:S. Karger AG    

年代:1993

数据来源: Karger