Gastric cytoprotective activity of endogenous 5-HT.

The role of endogenous serotinin in the formation of gastric damage was studied in rats. Stress ulcers were induced by ultrasounds, immobilization and immobilization plus cold. The damage of gastric mucosa was estimated (arbitrary scale) and serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in this tissue measured. In all examined groups of animals with gastric mucosal damages the lower levels of 5-HT and 5-HIAA in gastric mucosa were observed. In some experimental groups animals were treated with serotonergic receptor antagonists 30 min. before stress. The administration of ICS 205-930 (80 micrograms/kg), 5-HT3 receptor antagonist, and DAU-62855 (80 micrograms/kg), 5-HT4/5-HT3 receptors antagonist, reduced the intensity of stress gastric injuries. In contrast the administration of methysergide (8 mg/kg), 5-HT1/5-HT2 receptors antagonist, enhanced the stress gastric mucosa damage. 16, 16 dimethyl PGE2 (10 micrograms/kg) protected stomach against stress stimuli and accompanied increase of serotonin and 5-HIAA concentration in gastric mucosa was observed. Both 5-HT3/5-HT4 receptor antagonist had an additive cytoprotective effect when given in combination with PGE2 analog. In the presence of methysergide gastroprotective effect of PGE2 was abolished. The present studies demonstrate that cytoprotective effect of endogenous serotonin depends on 5-HT1 and 5-HT2 receptors stimulation in the gastric mucosa and the protective effect of prostaglandins depends partly on the regulation of serotonin metabolism.

Are histamine H1 receptors involved in ischaemia/reperfusion injury in rat heart?

During ischaemia, there was no apparent change in malondialdehyde (MDA) content in rat myocardium. However, reoxygenation resulted in a significant increase in MDA content. The changes evoked by ischaemia and reoxygenation were significantly attenuated by addition of fenistil (histamine H1 receptor antagonist). Enzymatic antioxidant systems were not significantly modified in the different periods of ischaemia and after 30 min of reoxygenation. It is suggested, that maintenance of an adequate endogenous antioxidant reserve during ischaemia may be important in recovery upon reoxygenation.

Inhibitory effect of tritoqualine on activation of latent polymorphonuclear leukocyte collagenase.

Treatment of rats with histamine releaser compound 48/80 caused changes in blood leukocyte populations. An increased number of PMN-leukocytes was observed. Tritoqualine only modestly reduced the number of granulocytes. In animals treated with compound 48/80 an activation of PMN-leukocyte latent collagenase of up to 80% was observed. This activation was partially inhibited (about 40%) in animals pretreated with tritoqualine. The results presented suggest that the beneficial effect of tritoqualine in allergic diseases may be in part connected with an indirect inhibition of collagenase activity.

Effect of alpha and beta adrenoreceptor antagonists on glucagon-induced inhibition of gastric acid secretion in cats.

The aim of the present study was to examine the effect of alpha and beta adrenoceptor blockade on gastric acid secretion, mucosal blood flow (GMBF) and catecholamine content of the gastric mucosa during glucagon-induced inhibition of gastric acid secretion. The secretory response to continuous infusion of pentagastrin (6 micrograms/kg/h) was reduced by regitine (0.5 mg/kg/h) and propranolol (25 micrograms/kg/h). Glucagon (25 ng/kg/h) further slightly decreased HCl secretion. GMBF was also significantly inhibited by regitine and propranolol. Administration of glucagon continued decreasing of the GMBF. By determining the change in the ratio of blood flow to secretory rate, this reduction in mucosal blood flow was found to be secondary to a fall in secretion. In these studies a concomitant increase in noradrenaline content of the gastric mucosa was observed: after regitine by 50%, after propranolol--by 32.5%, after these blockers given simultaneously--by 75%. The level of noradrenaline was higher after subsequent administration of glucagon. Our results indicate that more than one component is responsible for the inhibitory effect of glucagon on pentagastrin-stimulated gastric acid secretion.

Effect of glucagon on pentagastrin-stimulated gastric acid secretion and mucosal blood flow in cats.

The effect of glucagon given intravenously on pentagastrin-stimulated gastric acid secretion and gastric mucosal blood flow was studied in anaesthetized cats with gastric fistula. In parallel the catecholamines content in the gastric mucosa was measured. A continuous infusion of glucagon (25 ng/kg/h) caused a significant decrease of acid output (on the average by 33%) and gastric mucosal blood flow (by 40%). In these studies a concomitant increase in noradrenaline content of gastric mucosa was always seen (on the average by 108%). By determining the change in the ratio of blood flow to secretory rate a reduction in mucosal blood flow was found to be primary to the fall in secretion. The studies indicate that the inhibitory effect of glucagon on pentagastrin-stimulated acid secretion is due to restriction of mucosal blood flow. The results confirm also earlier data that glucagon stimulates the release of catecholamines.

Effect of low body temperature on gastric secretory activity in the guinea pig under urethane general anaesthesia.

Effect of low body temperature on gastric secretory activity in the guinea pig under urethane general anaesthesia. Acta Physiol. Pol., 1978, 29 (1): 61-66. The effect of low body temperature on spontaneous and histamine (H) stimulated or Nalpha Nalpha-dimethylhistamine (NDMH)-stimulated gastric secretion was investigated in the guinea pig under general anaesthesia with urethane. In normothermia NDMH had a stronger stimulatory action on acid secretion In hypothermia (30 degrees C and 25 degrees C) only NDMH showed some stimulating effect. The obtained results point to the necessity of strict controlling of body temperature in the experiments performed on animals under general anaesthesia and suggest that the lack of effect at low temperature may be connected with an inhibition of the processes of H side-chain methylation when the rate of metabolic processes in the organism has fallen.

Influence of some inhibitors of histamine metabolism on the gastric secretion.

Influence of some inhibitors of histamine metabolism on the gastric secretion. Acta Physiol. Pol., 1977, 28 (6): 515-520. The influence of inhibitors of histamine metabolism on histamine (H) and Nalpha Nalpha-dimethylhistamine (NDMH) stimulated gastric secretion was studied in guinea-pigs and cats. Inhibitors of monoamine oxidase (MAO) and diamine oxidase (DAO): N-oxide diacetylaminopyridine (AAP) and N-oxide 2 aminopyridine (AP) increased HCI secretion in the gastric juice after H and NDMH. Inhibitors of N-methyl transferase: amodiaquine (A) and quinacrine (Q) increased HC1 secretion in the gastric juice after H but not after NDMH. The lack of action of A and Q on NDMH-stimulated gastric secretion suggests, that in guinea-pig and cat NDMH is not methylated additionally at the imidazole ring and therefore, it is a stronger gastric secretagogue than histamine itself.