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G Coruzzi

Publications and source records attributed to G Coruzzi.

168 records · Page 10Linked to original sources
PubMedDate not supplied

Comparison between beta 3 and beta 2 adrenoceptor agonists as inhibitors of gastric acid secretion.

In order to investigate the role of beta 3 adrenoceptors in the regulation of gastric acid secretion we studied the effects of compound SR58611A (a selective agonist for atypical beta adrenoceptors), alone or in combination with beta-adrenoceptor antagonists, in the gastric fistula of a conscious cat. The effects of SR58611A were compared with those of clenbuterol, a selective agonist for beta 2 adrenoceptors. Intravenous infusion of SR58611A (0.3-3 mumol/kg/h) caused a dose-dependent, but partial, inhibition of the acid secretory response to 2-deoxy-D-glucose 100 mg/kg i.v., maximum effect not exceeding 40%. Clenbuterol (0.03-0.1 mumol/kg/h) caused a similar effect (maximum inhibition about 50%) at doses approximately 30 times lower. The acid secretion induced by the histamine H2-receptor agonist dimaprit (1 mumol/kg/h) was minimally affected by both beta adrenoceptor agonists. The inhibitory effect of SR58611A (3 mumol/kg/h) on 2-deoxy-D-glucose-induced acid secretion was not modified by pretreatment with the non-selective beta 1- and beta 2-adrenoceptor blocker propranolol, administered at doses (1.5 mumol/kg iv) that completely blocked the inhibitory effect of clenbuterol (0.1 mumol/kg/h). In contrast, bupranolol (10 mumol/kg i.v.) (a drug endowed with beta 3 antagonistic properties) prevented the inhibitory effects of both SR58611A and clenbuterol. The present data provide functional evidence that, besides beta 2-, also beta 3-adrenoceptors can have negative effects on gastric acid secretion, particularly when it is stimulated by indirect stimuli, like 2-deoxy-D-glucose. This gastric antisecretory activity may represent an additional mechanism for the physio-pharmacological control of gastric acid secretion.

Adrenergic beta-2 Receptor Agonists↗
PubMedDate not supplied

Antisecretory and gastroprotective activities of compounds endowed with H2 antagonistic and nitric oxide (NO) donor properties.

In spite of the well recognized gastric antisecretory activity, the gastroprotective potential of histamine H2 receptor antagonists is controversial. Most clinical studies in fact indicate that these drugs do not substantially protect the gastric mucosa from aggressive factors. Nitric oxide (NO) has been recently recognized as a fundamental mediator in gastric defence mechanisms, due to its ability to increase gastric mucosal blood flow and mucus production and to inhibit neutrophils adherence to endothelial cells. The aim of this study was to investigate the gastroprotective and H2 receptor antagonistic activity of a series of lamtidine analogues which contain different NO-releasing moieties (furoxan, nitroxy and nitrosothiol). These compounds were tested, in comparison with related H2 antagonists devoid of NO-donor structures, in different H2 receptor assays and in the conscious rat against 0.6 N HCl-induced gastric lesions. All the compounds tested were able to antagonize histamine-mediated responses at cardiac and gastric H2 receptors; however, furoxan and nitroxy derivatives were 10-fold less potent than the analogues devoid of NO-donor properties. By contrast, NO-donor compounds were more active than reference H2 antagonists as gastroprotective agents against mucosal injury induced by 0.6 N HCl. Among the different NO-donor moieties, the furoxan group conferred to the H2 antagonist molecule the highest gastroprotective potential; this finding closely correlates with the characteristics of NO release. In conclusions, lamtidine-analogue H2 antagonists combined with NO-donor moieties are endowed with gastric antisecretory and protective activity and could be the prototypes of a new class of anti-ulcer drugs. Finally, the furoxan NO donor group seems to be the most favourable among the different moieties tested.

Animals↗
PubMedDate not supplied

Histamine H3 receptors in the guinea pig ileum: evidence for a postjunctional location.

The effect of the selective histamine H3 receptor agonists (R)alpha-methylhistamine, (R)MHA and immepip (IMM) on intestinal smooth muscle contractility was investigated on isolated cells from the longitudinal muscle of the guinea pig ileum. (R)MHA (10(-13)-10(-8) M) and IMM (10(-13)-10(-8) M) did not significantly modify the basal length of intestinal cells; in contrast both agonists (10(-15)-10(-11) M) prevented the contraction produced by acetylcholine (10(-7) M). The (S)-isomer of alpha-methylhistamine, (S)MHA, was inactive both on basal contractility and on acetylcholine-induced contractions. The relaxant effect of (R)MHA was not modified by famotidine (10(-7) M), but totally prevented by the selective H3 receptor antagonist clobenpropit (10(-8) M), which per se did not modify either basal contractility or the contractile response to acetylcholine. These data indicate that inhibitory histamine H3 receptors are present on smooth muscle cells of the guinea pig ileum and can be activated by very low concentrations of selective agonists. It is not clear, however, whether they can have a functional importance in the regulation of intestinal contractility in an intact system.

Acetylcholine↗
PubMedDate not supplied

Histamine H3 receptors: an overview.

Histamine H3 receptors represent a new class of prejunctional receptors, which, first described as modulators of histamine synthesis and release in the central nervous system, were subsequently found to occur also in peripheral tissues. They may behave both as autoreceptors located in histaminergic neurons and as heteroreceptors localized in adrenergic, cholinergic, serotoninergic and NANC nerve endings. As far as the gastrointestinal tract is concerned, H3 receptors seem to negatively control gastric acid secretion induced by endogenous cholinergic stimuli as well as gastrointestinal motility, as observed in different isolated preparations electrically stimulated. So far experimental evidence suggests that these receptors are absent in the effector organs. The most selective agonist and antagonist of H3 receptors are (R) alpha-methylhistamine and thioperamide, respectively; however, a lot of similar compounds are being synthesized in a few laboratories. It is easy to foresee that in the near future the availability of such substances will help the investigators in enlarging our knowledge in this interesting field.

Animals↗
PubMedDate not supplied

Gastric antisecretory activity of telenzepine, a new M1-selective muscarinic antagonist: comparison with pirenzepine.

The new M1-receptor antagonist telenzepine has been studied for its antisecretory effect in different in vitro and in vivo experimental models in comparison with pirenzepine. Telenzepine was found to be from 3 to 10 times more potent than pirenzepine in inhibiting bethanechol-, pentagastrin- and dimaprit-induced acid secretion in the conscious gastric fistula cat. Also, in the lumen-perfused stomach of the anaesthetized rat, telenzepine was more active than pirenzepine as an inhibitor of bethanechol-induced acid secretion; the inhibitory effect of telenzepine lasted more than 3 hr, while that of pirenzepine disappeared within 1 hr. In the isolated gastric fundus from immature rats, telenzepine and pirenzepine did not modify the spontaneous acid secretion, whereas both drugs caused a competitive inhibition of bethanechol-induced acid secretion (pA2 values were 7.96 and 6.81 for telenzepine and pirenzepine, respectively). These data indicate that telenzepine is a potent antisecretory agent both in vitro and in vivo.

Anesthesia↗