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C Blandizzi

Publications and source records attributed to C Blandizzi.

58 records · Page 4Linked to original sources
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Peripheral cholecystokinin A and cholecystokinin B receptors mediate stimulation of gastric pepsinogen and acid secretion following intracerebroventricular injection of cholecystokinin-8-sulphate.

BACKGROUND: Peptides of cholecystokinin family regulate various physiological actions by acting at level of central nervous system. AIMS: To: 1) investigate possible influence of central cholecystokinin pathways on gastric pepsinogen and acid secretions; 2) characterize pharmacological profile and location of cholecystokinin receptor subtypes involved in gastric effects of centrally applied cholecystokinin-8-sulphate (cholecystokinin-8S). METHODS: Urethane-anaesthetized rats were subjected to continuous perfusion of gastric lumen. Pepsin levels in perfusate were determined by enzymatic assay based on spectrophotometric measurement of products generated by peptic digestion of bovine haemoglobin. Acidity was measured by automatic potentiometric titration of hydrogen ions. RESULTS: Following intracerebroventricular injection, cholecystokinin-8S increased both pepsinogen and acid output. In addition, intravenous cholecystokinin-8S stimulated peptic and acid secretions more promptly and at lower doses than after central injection. Stimulant effects of centrally applied cholecystokinin-8S were not affected by intracerebroventricular injection of devazepide (cholecystokinin A receptor antagonist) or L-365,260 (cholecystokinin B receptor antagonist) or by bilateral vagotomy. However, intravenous devazepide partly antagonized pepsigogue action of intracerebroventricular cholecystokinin-8S without affecting its acid hypersecretory effect, whereas after intravenous injection of L-365,260 peptic hypersecretion evoked by intracerebroventricular cholecystokinin-8S was partially prevented and acid response was completely blocked. Similar effects were exerted by intravenous devazepide and L-365,260 against intravenous cholecystokinin-8S. A complete blockade of pepsigogue effects induced by intracerebroventricular or intravenous cholecystokinin-8S was obtained after combined intravenous treatment with devazepide plus L-365,260. Gastric hypersecretory effects of intravenous cholecystokinin-8S were not modified by bilateral vagotomy. CONCLUSIONS: Increase in pepsinogen output evoked by centrally applied cholecystokinin-8S does not depend on interaction with central nervous sites. Following central or parenteral injection of cholecystokinin-8S, increase in peptic secretion would result from activation of both peripheral cholecystokinin A and B receptors presumably located at the level of gastric mucosa.

Analysis of Variance↗
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[A selective antimuscarinic agent: pirenzepine. Review of its pharmacologic and clinical properties].

The heterogeneity of muscarinic receptors has been well supported by differential characteristics between pirenzepine and atropine both in receptor binding and in whole tissue pharmacology studies. Under these conditions pirenzepine has been classified as a selective receptor antagonist with high affinity for M1 receptors. The antisecretory properties of pirenzepine on gastric acid and pepsin secretion may be attributed to the antagonistic activity of the drug on muscarinic M1 receptors of gastric intramural plexuses, whereas the effect on parietal muscarinic M2 receptors seems of less importance. Additional inhibitory mechanisms on gastric secretion may be represented by pirenzepine-induced increase in somatostatin release from gastrointestinal system. Significant cytoprotective properties of pirenzepine have been observed on a variety of experimentally induced peptic ulcerations. This protective activity may be due to pirenzepine-induced increase in gastric mucosal blood flow as well as to the increase in gastric transmural electric potential difference. In accordance with this pharmacodynamic profile of pirenzepine, numerous clinical studies have revealed its efficacy in the treatment of both duodenal and gastric ulcerations. In addition to this, the clinical usefulness of the drug has been demonstrated in Zollinger-Ellison syndrome, in stress ulceration, in acute gastrointestinal bleeding as well as in gastritis, duodenitis and non-ulcer dyspepsia. In most of the studies pirenzepine has been found to be well tolerated with a low incidence of antimuscarinic effects which may occur at salivary, ocular, cardiac and urinary sites. The clinical use of pirenzepine alone or in association with H2 blockers is recommended in the treatment of peptic ulcer patients, in the case of acute gastrointestinal haemorrhage and in patients non responders to H2 antagonists.

Animals↗
PubMedDate not supplied

Pirenzepine prevents cysteamine-induced formation of gastroduodenal ulcers and reduction of mesenteric circulation.

The effects of pirenzepine on gastric and duodenal ulceration and barrier mucus levels, as well as on changes of superior mesenteric artery diameter caused by cysteamine, were investigated in rats and compared with those of atropine. Cysteamine induced severe gastric and duodenal ulcers and decreased both barrier mucus levels and mesenteric blood flow. Pirenzepine reduced gastric and duodenal ulceration induced by cysteamine. Moreover, pirenzepine significantly increased basal mesenteric artery diameter and fully prevented cysteamine-induced decrease in mesenteric blood flow. Under the same conditions, atropine failed to prevent gastric and duodenal ulceration or mesenteric artery changes caused by cysteamine. Both pirenzepine and atropine were without any effect on cysteamine-induced inhibition of gastric and duodenal barrier mucus levels. The present results are consistent with the view that pirenzepine protects against gastroduodenal ulceration caused by cysteamine by increasing blood flow at the level of the ulcerated mucosa. The higher affinity of pirenzepine for the muscarinic receptors of sympathetic ganglia may explain the difference between the effects of pirenzepine and atropine. In addition to this, the measurement of superior mesenteric artery diameter changes may represent an accurate and reproducible method, suitable for studying the gastrointestinal protective mechanisms of the drugs.

Animals↗