摘要:

Myotropic effects of various peptides were measured in three isolated vessels, the dog carotid artery, the rabbit pulmonary artery and the rat portal vein in the absence and in presence of several peptidase inhibitors, in order to evaluate the interference by metabolism with the peptides’ biological activities. After adequate controls, captopril (4.6·10–6 mol/l), thiorphan (1.0·10–6 mol/l), phosphoramidon (4.6·10–6 mol/l), chymostatin (1 mg/l), bestatin (8.1·10–6 mol/l) or bacitracin (1.4·10–5 mol/l) were left in contact with the tissues for 20–40 min to inhibit tissue peptidases before measuring again the biological effects of the various peptides. In some experiments, mergetpa (5.4·10–6 mol/l) was used. All peptidase inhibitors were inactive on their own and only captopril potentiated the effects of substance P, neurokinins, bradykinin and inhibited angiotensin I in two preparations, the dog carotid artery, the rat portal vein, and, excluding bradykinin, also in the rabbit pulmonary artery. Captopril and thiorphan significantly potentiated the maximal response of the rat portal vein to substance P and mergetpa inhibited completely the effect of bradykinin on the rabbit pulmonary artery. The present findings suggest that the most active proteolytic enzyme interfering with the biological effects of vasoactive peptides on three isolated vessels is the angiotensin-converting

ISSN:0031-7012    

DOI:10.1159/000138658

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Neurokinins, bradykinin and angiotensins were tested in isolated urinary bladder of the guinea pig, the hamster and the rat, in the absence and in presence of a variety of peptidase inhibitors in order to establish if peptide degradation interferes with the bladder contractions elicited by the three types of peptides. Indeed, the effects of neurokinins, bradykinin and angiotensin I in the guinea pig bladder were significantly enhanced by captopril (4.6·10–6 mol/l), chymostatin (1 mg/l), phosphoramidon (4.6·10–6 mol/l) and thiorphan (1.0·10–6 mol/l), while only captopril was found to potentiate the effects of the same peptides in the rat bladder. The four peptidase inhibitors, as well as bacitracin were found to modify the responses of the hamster urinary bladder to one or another or to all three groups of peptides and to DiMeC7. The present results suggest that the urinary bladders of various species have different types of active proteolytic enzymes: only the angiotensin-converting enzyme appears to be present in the rat bladder, while the same enzyme and possibly two additional endopeptidases interfere with the myotropic effects of neurokinins, kinins and angiotensins in the guinea pig and the hamster

ISSN:0031-7012    

DOI:10.1159/000138659

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Baclofen, γ-amino-β-hydroxybutyric acid (GABOB), calcium hopantenate (HOPA) and citicoline, which are clinically used for improving cerebral insufficiency, were tested for their effects on gastric acid secretion in the perfused stomach of urethane-anesthetized rats. These drugs were administered intravenously or subcutaneously. They produced a significant increase in gastric acid secretion, although the extents in increase were different. The duration of action was 1–2 h. The potency order was baclofen > GABOB ≥ citicoline ≥ HOPA. The stimulatory response to each drug was completely inhibited by atropine. In contrast, the peripheral secretory activity of each drug was not demonstrated in the isolated lumen-perfused stomach of mice. These results indicate that all the tested drugs produce an increase in gastric acid secretion probably via central cholinergic activation and that gastric acid stimulation by compounds improving the cerebral insufficiency might be included in side effects in their clini

ISSN:0031-7012    

DOI:10.1159/000138660

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Comparative effects of CV-6209, a potent and specific platelet activating factor (PAF) antagonist, on PAF-acether-, carrageenin-, histamine-, serotonin-, compound 48/80-, dextran-, zymosan A- and arachidonic acid-induced rat paw edema were investigated. CV-6209 has proven to be effective in PAF-induced edema, but it also showed a significant activity in other models of paw edema, except those induced by zymosan A and arachidonic acid. Other drugs tested, namely indometacin, mepyramine, methysergide and nordihydroguaiaretic acid showed a more selective inhibitory profile. These results suggest an important role of PAF in the inflammatory process caused by intraplantar injection of different phlogogens in the rat paw.

ISSN:0031-7012    

DOI:10.1159/000138661

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Adult male Sprague-Dawley rats weighing between 170 and 204 g and maintained under controlled lighting and temperature conditions were used in this experiment. One group of animals was treated with 30 mg/kg of cocaine hydrochloride and the other group with saline. Rats were decapitated 20 min after cocaine injection and their brains were removed and the different regions including the medulla, pons, midbrain, cerebellum, hypothalamus, thalamus, hippocampus, and the cortex were dissected. All brain regions were assayed for choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities. The results obtained indicated that the administration of cocaine was associated with significant increases (p < 0.01) in AChE activity in the medulla, pons, midbrain, hypothalamus, thalamus, and also in the hippocampus (p < 0.05). A significant decrease in ChAT activity was found in the pons (p < 0.01), hypothalamus, and thalamus (p < 0.05), while a significant increase in ChAT activity was found in the cortex (p < 0.05). The results suggest that the changes in general activity followed by stereotypic behavior may be related to the changes in the levels of cholinergic enzymes in specific brain regions.

ISSN:0031-7012    

DOI:10.1159/000138662

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Nicotinic acetylcholine receptors are found on both muscle tissue and neuronal tissue, including adrenal chromaffin cells. Certain drugs, such as the noncompetitive ion-channel blockers and the vinca alkaloids, have been demonstrated to interact with muscle-type nicotinic receptor-associated ion channels. The objectives of these studies were: (1) to determine the effects of the noncompetitive blockers of the nicotinic receptor-associated ion-channel drugs on adrenal chromaffin cells, and (2) to establish whether the vinca alkaloids and the ion-channel drugs have similar actions on adrenal nicotinic receptors. The ion-channel drugs, adiphenine, tetracaine, quinacrine, amantadine, lidocaine and procaine, inhibited receptor-stimulated catecholamine release from cultured adrenal chromaffin cells in a concentration-dependent manner (IC50S: 2, 4, 6, 41, 55 and 87 μM, respectively). The inhibitory effects of these drugs appeared to be noncompetitive. These drugs had little or no effects on catecholamine release stimulated by depolarizing concentrations of K+ or on basal release. Our results demonstrate that the ion-channel blockers interact with adrenal nicotinic receptors in a manner similar to their interaction with muscle-type nicotinic receptors and they interfere with adrenal receptor function in a manner similar to the vinca alkaloids

ISSN:0031-7012    

DOI:10.1159/000138663

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

After a rapid increase in infusion rate of adrenaline to elevate the initial heart rate by more than 15 %, a continuous infusion was sustained in order to maintain elevated adrenaline plasma levels. At the end of the first phase of the experiment, the thrombocyte α2-adrenoceptor number (determined by radioligand binding) was significantly lowered. After the second part of the experiment, a further significant decrease in the density of binding sites was observed, while elevated adrenaline plasma levels were kept constant. The decrease in the number of binding sites was accompanied by a slight increase in affinity of the radioligand. Serum potassium concentration significantly decreased during the experiment, while other serum electrolytes showed no significant alterations

ISSN:0031-7012    

DOI:10.1159/000138664

出版商:S. Karger AG    

年代:1990

数据来源: Karger

摘要:

Iron has been implicated in the inflammatory process. In this paper we studied the modulating inflammatory activity of iron in the carrageenan-induced granuloma pouch, taking indometacin as a standard anti-inflammatory drug. Sprague-Dawley rats were injected subcutaneously with desferrioxamine (100 mg/kg) and indometacin (5 mg/kg) for 3 consecutive days before granuloma induction, followed by a daily administration in the granuloma pouch until the day before death. We determined the granuloma weight and assayed in the exudate: volume, number of leukocytes, PGE2 levels and loosely bound iron content at 1 (acute inflammation) and 6 days (chronic inflammation) after granuloma induction. Our results show a dual effect of desferrioxamine, inflammatory in the acute phase and anti-inflammatory in the chronic phase. These results are discussed in relation to chemotaxis and to the potential role of iron on oxygen free radical production, collagen synthesis and hydroperoxide generation, while indometacin acts through the cyclooxygenase pathway.

ISSN:0031-7012    

DOI:10.1159/000138665

出版商:S. Karger AG    

年代:1990

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138667

出版商:S. Karger AG    

年代:1990

数据来源: Karger