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Biomedical subjects

G Coruzzi

Publications and source records attributed to G Coruzzi.

At least 109 records · Page 6Linked to original sources
PubMed1986

Inhibitory effect of famotidine on cat gastric secretion.

The inhibitory effect of the novel H2 receptor antagonist famotidine was studied in conscious gastric fistula cats against dimaprit-induced hypersecretion, in comparison with ranitidine. On the secretory plateau induced by dimaprit (2 mumol kg-1 h-1) famotidine (0.05-0.2 mumol kg-1 i.v.) exerted a dose-dependent inhibitory effect, being approximately 4.5 times as potent as ranitidine (ID50 values were 0.067 +/- 0.015 and 0.30 +/- 0.025 mumol kg-1 for famotidine and ranitidine, respectively). No significant differences were found between the two drugs, as for the time-course of the inhibitory effect. Famotidine (0.01-0.32 mumol kg-1 h-1) caused a parallel displacement of the dose-response curve to dimaprit to the right, without reducing the maximum response to the stimulant, thus behaving as a competitive antagonist, like ranitidine. pA2 values for famotidine and ranitidine were 7.95 and 6.92, respectively. In the same range of doses famotidine dose-dependently reduced also the secretory response to histamine. From these data it was concluded that famotidine is a potent histamine H2 receptor antagonist in the cat gastric mucosa; moreover, conversely from "in vitro" data, the antagonism was surmountable even at the highest doses tested. In vivo experiment, therefore, did not reveal any particular feature of this compound, apart from the undoubtedly high potency, in comparison with other members of the family.

Animals↗
PubMed1986

Effects of Ca2+ ions on gastric acid secretion by the rat isolated stomach.

The role of Ca2+ in the stimulatory action of histamine has been evaluated in the isolated gastric fundus from immature rats, by changing the concentration of calcium ions in the bathing solutions. Lowering Ca2+ to 1.2 mM greatly enhanced the secretory response to histamine, while leaving unaffected that to the H2-receptor agonist, dimaprit. The effect of histamine was competitively antagonized by ranitidine (pA2 = 6.78) in normal solutions; conversely in 1.2 mM Ca2+, the antagonism by ranitidine became unsurmountable. Basal rates of acid secretion did not change in low Ca2+ solutions, whereas they were reduced approximately by 50% in Ca2+-free media. Finally, the secretory response to theophylline was significantly lower in low Ca2+ solutions in comparison with that in control conditions. From the above results it may be concluded that changes in the concentration of Ca2+ ions caused different changes in the secretory response of the rat stomach in the various experimental conditions. The marked enhancement of the response to histamine observed in low Ca2+ is unlikely to be connected with H2-receptors, as suggested by the lack of interference in the response to dimaprit, but it could be related to intracellular mechanisms (H+/K+-ATPase, carbonic anhydrase activation etc.).

Adenylyl Cyclases↗
PubMed1986

Effect of omeprazole on gastric acid secretion by the rat isolated stomach.

The inhibitory effect of omeprazole has been investigated on the isolated gastric fundus from immature rats. Omeprazole (10(-7)-10(-5) M) inhibited basal acid secretion, conversely from H2-receptor antagonists, antimuscarinic compounds and calcium antagonists; the effect was mimicked only by KSCN (3 X 10(-4)-3 X 10(-2) M). Omeprazole (10(-6)-10(-5) M) caused an insurmountable antagonism of the hypersecretion induced by histamine and bethanechol, whereas it competitively antagonized the secretory response to isoprenaline and dibutyryl cAMP. Experiments carried out in low calcium media showed that calcium ions did not significantly affect the inhibitory potency of omeprazole when tested on basal acid secretion, whereas low calcium solutions enhanced the action of omeprazole against histamine-induced hypersecretion. The above data confirmed the potent antisecretory activity of omeprazole in different experimental conditions in which the common antisecretagogues are without effect and pointed out the novel site of action in the control of gastric acid secretion at intracellular level.

Animals↗
PubMed1986

Bay K 8644 and acetylcholine: different interaction with calcium ions in the rat duodenal muscle.

The contractile effect of the dihydropyridine analogue Bay K 8644, recently described as a Ca2+-agonist, has been evaluated in the rat isolated duodenal muscle in comparison with that of acetylcholine. Bay K 8644 (3 X 10(-10)-10(-6) mol/l) increased the duodenal motility, whereas it behaved as an inhibitor when tested at high concentrations (greater than 10(-6) mol/l). Bay K 8644 was more potent than acetylcholine (threshold concentration 3 X 10(-10) vs. 10(-8) mol/l) but less efficient. The contractile responses to Bay K 8644 and acetylcholine were reduced in calcium-free medium and abolished by addition of 1 mmol/l EGTA. In some K+-depolarized tissues, however, a contractile response to Bay K 8644 was still observed. The effects of Bay K 8644 and acetylcholine were antagonized by nifedipine and verapamil; however, a competitive antagonism was observed only for the interaction Bay K 8644-nifedipine (pA2 = 9.86). The contraction induced by Bay K 8644 was noncompetitively antagonized by low concentrations of atropine (10(-7) mol/l); Bay K 8644 (10(-7) mol/l) did not modify the response to acetylcholine, while inhibiting it at higher concentration (10(-5) mol/l); in addition, it was able to enhance the response to endogenous acetylcholine, released by field stimulation. The above results indicated that Bay K 8644 and cholinergic stimuli are strong activators of the duodenal motility in vitro. The interference of Bay K 8644 with the cholinergic system, observed in both unstimulated and electrically stimulated strips, suggested a novel site of action of this compound in the gastrointestinal muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Non-antisecretory activities of H2 antagonists.

Besides the main effect of the H2 antagonists--that is, the inhibition of gastric acid secretion--these drugs possess several other pharmacological activities, which in most cases may be evident only for doses higher than those required to produce the H2 blockade. The non-secretory activities of the H2 antagonists may be classified into true side effects--that is, those independent of the primary action, which may or may not depend on the primary action. They concern the central and autonomic nervous systems, cardiovascular and endocrine systems, digestive system (gut, liver, pancreas), immune system, and so forth. It is obvious that when the actions of the different H2 blockers are completely at variance with regard to the same factor (cimetidine increase the TSH response to TRH, whereas ranitidine decreases it; ranitidine stimulates gastrointestinal motility, whereas oxmetidine inhibits it; ranitidine increases the exocrine pancreatic response to cholecystokinin, whereas oxmetidine decreases it; metiamide and cimetidine increase the activity of histamine methyltransferase, whereas burimamide decreases it), this is a clear demonstration that we are dealing with non-specific effects rather than with H2-receptor blockade. All these effects may be of interest because sometimes they may be useful in potentiating the primary action, and sometimes they may represent adverse reactions. In any case, they characterize pharmacologically the individual molecules of the family.

Autonomic Nervous System↗
PubMed1986

Pharmacological study of basal acid secretion by the rat isolated fundus preparation.

The rat isolated stomach preparation secretes acid in the absence of exogenous stimulants. This basal secretion of acid was unaffected by high concentration of antagonists to stimulated secretion in this preparation and by TTX. Basal secretion was inhibited by omeprazole (10(-7)-10(-5) M), KSCN (10(-4)-10(-2) M) and to a lesser extent by somatostatin (10(-6)-10(-5) M) but not by verapamil (3 X 10(-4) M), nifedipine (3 X 10(-4) M) and trifluoperazine (10(-3) M). Two long-acting H2-antagonists, oxmetidine and SKF 93479 (10(-5)-10(-4) M) inhibited basal secretion by a mechanism not involving an action at H2-receptors. It is concluded that basal secretion in this in vitro preparation is independent of the endogenous release of known stimulants of acid secretion and activity of the intrinsic nervous system.

Animals↗
PubMed1985

The action of two mast cell stabilising agents and verapamil on rat gastric acid secretion in vitro.

The actions of two mast cell stabilising agents, FPL 52694 and disodium cromoglycate and the Ca2+ channel antagonist verapamil on acid secretion by the rat isolated stomach have been studied. FPL 52694 (1-5 mM) in the serosal medium stimulated acid secretion. This was antagonised by prostaglandin E2 but not by atropine, metiamide, propranolol or tetrodotoxin. FPL 52694 (1-5 mM) in the mucosal medium had an inhibitory effect on basal acid secretion and that stimulated by pentagastrin and histamine. The inhibition reversed only slowly after removal of FPL 52694. Disodium cromoglycate and serosal application of verapamil had no significant effects on acid output. Removal of calcium from the bathing solutions and mucosal verapamil inhibited basal secretion. Topically applied, FPL 52694 is a potent inhibitor of acid secretion in vitro. This effect may involve an action upon the availability of calcium to the tissue. The stimulatory effects of serosal FPL 52694 are discussed in relation to previous in vivo findings.

Animals↗
PubMed1985

The stimulatory action of the calcium channel agonist Bay K 8644 on isolated duodenal muscle. Antagonism by nifedipine and verapamil.

The action of the novel dihydropyridine analogue Bay K 8644 has been evaluated on the rat isolated duodenal muscle. Bay K 8644 (0.3 nmol/l to 1 pmol/l) increased both the tone and the phasic movements of the duodenum; the maximum response was about 60% of that to acetylcholine. Nifedipine (30 nmol/l) induced a parallel shift of the concentration-response curve to this compound to the right, without depressing the maximum response; conversely, verapamil (30 nmol/l) caused an insurmountable antagonism. Incubation of the strips in Ca2+-free medium reduced the contractile response to the calcium agonist. The spasmogenic effect of Bay K 8644 was inhibited by atropine (0.1 pmol/l) which caused a significant reduction in the maximum response to the compound. The competitive interaction between Bay K 8644 and nifedipine is consistent with an action at the same dihydropyridine binding site in the calcium channel and suggests that these compounds could be selective probes for detecting the dihydropyridine receptor also in the intestinal smooth muscle. The sensitivity of the contractile effect of Bay K 8644 to atropine may indicate an action of this compound in the cholinergic system, probably mediated by a release of acetylcholine from the nerve terminal rather than due to a direct stimulatory action at muscarinic receptors in the smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Pharmacology of the treatment of peptic ulcer disease.

Anti-ulcer drugs may be classified according to their site and/or mechanism of action as: corticohypothalamic drugs; antisecretory drugs which may be anticholinergic agents (both classical atropine-like compounds and pirenzepine) or antagonists of the H2-receptors; antacids; agents which protect the mucosa; and gastric muscle stimulants. New groups of compounds with different pharmacokinetics and mechanisms of action are currently being investigated, and it is possible that they will represent an alternative to, or a substitute for, the present widely used anti-ulcer drugs. Among the new drugs, synthetic prostaglandins are probably the most interesting compounds, having potent antisecretory activity together with important cytoprotective properties. Another interesting group are the inhibitors of H+/K+-ATPase such as the substituted benzimidazoles, among which omeprazole is characterized by potent and long-acting antisecretory activity. Theoretically, other drugs such as calcium-entry blockers and synthetic somatostatin analogs deserve consideration although results obtained are preliminary.

Aluminum↗
PubMed1985

Histamine H2-receptor agonists and antagonists on pancreatic exocrine secretion of the dog.

The use of H2-receptor agonists and antagonists allowed us to establish that histamine H2-receptors are present in pancreatic exocrine tissue and their stimulation caused a dose-dependent increase in pancreatic juice. The fact that H2-antagonists from one side and aminoguanidine from the other were unable to modify basal levels of pancreatic secretion, seems to minimize a role for H2-receptors in the regulation of pancreatic secretion. On the other hand H2-antagonists modified ceruletide-induced secretion in different ways according to the different molecules. Ranitidine strongly potentiated whereas cimetidine, oxmetidine and mifentidine slightly inhibited the effect of ceruletide. The stimulatory effect of eserine and the inhibitory effect of atropine indicate a cholinergic interference in the action of ceruletide. Therefore the potentiating effect of ranitidine may be related to its cholinomimetic action and the inhibitory effect of the other H2-antagonists may be connected with an anticholinergic effect. However, the potentiating effect of aminoguanidine on ceruletide-induced secretion may indicate a possible role for histamine in the response to ceruletide.

Animals↗
PubMed1985

Histamine H2 receptor antagonists may modify dog intestinal motility independently of their primary action on the H2 receptors.

Various histamine H2 receptor antagonists were tested for their possible effects on intestinal motility of the dog both "in vivo" and "in vitro". They were found to behave quite differently from one another: ranitidine exerted a small atropine-sensitive stimulatory effect by itself and strongly potentiated the stimulatory action of compounds which interfere with the cholinergic system thus confirming its cholinomimetic direct and/or indirect activities. Cimetidine and mifentidine were ineffective even at very high doses. Oxmetidine exerted an inhibitory effect independently of the kind of the stimulant agent and this suggested a direct effect on the smooth muscle. The different effects elicited by the above H2 antagonists indicate that their action on the intestinal motility is completely independent of the H2 blockade. This was furtherly confirmed by the lack of effect shown by the H2 receptor selective agonists, dimaprit and impromidine. The motor effects of ranitidine were, so far, the only ones which have been encountered, in different conditions, also in humans.

Acetylcholine↗
PubMed1985

Rat gastric secretion "in vitro": interaction between histamine and various antisecretagogues acting by different mechanisms.

The interaction between histamine and various antisecretagogues acting by different mechanisms has been investigated in the isolated fundus from the rat stomach. Histamine evoked a concentration-dependent stimulatory effect which was competitively antagonized by the H2-receptor antagonist, ranitidine and non competitively by the H+/K+-ATPase inhibitor, omeprazole. The histamine induced secretion was highly resistant to the action of the calcium entry blocker verapamil, somatostatin and KSCN, but some inhibition was obtained with the calmodulin antagonist, trifluoperazine. Removal of calcium ions from the bathing media (both mucosal and serosal) greatly enhanced histamine-induced gastric secretion. The results suggest that the relationship between receptor stimulation and the intracellular events leading to acid secretion is far from being elucidated.

Animals↗
PubMed1985

Stimulatory action of (beta-Asp9) ceruletide on dog pancreatic exocrine secretion.

The synthetic analog of ceruletide, (beta-Asp9) ceruletide, which in previous studies was found to retain some central effects of ceruletide with virtually no effect on gallbladder contraction, was studied for its stimulatory effect on pancreatic secretion. This peptide was shown to induce an increase in the volume of pancreatic juice similar to that provoked by the parent compound. Its activity was 4% of that of ceruletide, as regards volume, dry residue and protein content of the pancreatic juice. It was concluded that the dissociation between central and peripheral effects concerned only the gallbladder contractility, since its potency as a pancreatic stimulant was of the same order of magnitude as that shown on the central nervous system.

Amino Acid Sequence↗
PubMed1985

Action of different agonists and antagonists of the cholinergic system on the rat lower esophageal sphincter.

Several compounds acting on the cholinergic system at different levels were tested for their stimulatory or inhibitory effects on the isolated lower esophageal sphincter (LES) of the rat. Results obtained with acetylcholine, bethanechol and compound McN-A343 on the one hand and atropine, pirenzepine, ganglion blocking agents and tetrodotoxin on the other, suggested that LES contraction was associated mainly with the stimulation of post-synaptic muscarinic receptors. Nicotinic receptors (both ganglionic and muscular) seem to have a minor role, if any.

Animals↗
PubMed1985

Characterization of cholinoreceptors in the rat urinary bladder by the use of agonists and antagonists of the cholinergic system.

The effects of stimulatory and inhibitory compounds acting on both nicotinic and muscarinic receptors have been evaluated in the isolated urinary bladder from adult and immature (14-18 days old) rats. Acetylcholine and bethanechol were found to induce concentration-dependent contractions which were inhibited by atropine and pirenzepine; compound McN-A-343 had a negligible contractile activity whereas DMPP had no effect at all. Responses to electrical field stimulation were abolished by tetrodotoxin (3 X 10(-8) M), enhanced by eserine (10(-8) M) and scarcely affected by hexamethonium (10(-3) M), trimethaphan (10(-3) M) and d-tubocurarine (10(-3) M). Atropine, pirenzepine and DMPP induced only a partial inhibition (50%) of the twitch response, whereas compound McN-A-343 caused a concentration-dependent inhibitory effect which was maximum (100% inhibition) at 10(-2) M. No significant differences were found between results obtained in immature and adult animals as regards either the stimulatory or the inhibitory compounds tested. It was concluded that postjunctional muscarinic receptors were responsible for the stimulatory responses observed, whereas an additional involvement of unknown mechanisms, probably not related to the cholinergic system, was suggested by the peculiar results obtained with DMPP and compound McN-A-343 on electrically-stimulated urinary bladder. Whatever the mechanisms involved, however, they are already present at the first stage of postnatal development.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗