Effects of Β‐adrenoceptor Drug Stimulation on Various Models of Gastric Ulcer in Rats

Abstract

1 Experiments were designed to evaluate the effect of the pharmacological activation of fadrenoceptors on various models of gastric ulcer in the rat.2 Pretreatment with the P-adrenoceptor stimulant drugs, isoprenaline or salbutamol, significantly inhibited stress-induced gastric ulcers. This anti-ulcer effect was abolished by propranolol but not by atenolol, suggesting that P2-adrenoceptors mediate this response.3 In the pylorus-ligation model, salbutamol inhibited lesion formation and reduced the intragastric content of hydrogen ions, histamine and pepsin although the latter was only affected with the higher dose of salbutamol.4 Salbutamol also prevented the ulcerogenic action on the gastric mucosa of an exogenously perfused artificial gastric juice, showing that the anti-ulcer effect is not necessarily dependent on acid inhibition. 5 Salbutamol also reduced the formation of acute ulcers induced by various iatrogenic means (histamine, polymyxin B, reserpine and indomethacin). 6 Long-term treatment with salbutamol accelerated the healing of experimental chronic gastric ulcer.7 In anaesthetized rats, salbutamol produced a dose-related increase in mucosal blood flow which may contribute to its mode of action.8 It is concluded that P-adrenoceptor agonists exert preventive and curative effects on gastric damage induced in the rat. This effect seems specific and mediated through P-adrenoceptor activation.

Evaluation of the Effects of Nicorandil on Experimentally Induced Gastric Ulcers

“…Therefore, it can be said that in addition to a reduction in total acidity, a reduction in pepsin activity also contributes towards its antiulcer activity. The result is supported by reports [27,28] suggesting that the secretion of pepsin and acid is affected by drugs through similar mechanisms. This shows that Ca 2+ is very much involved in the physiological secretion of pepsin.…”

“…The effects of nicorandil on total acidity and pepsin activity were prevented by glibenclamide, whereas glibenclamide alone increased total acidity and pepsin activity. Thus the effects of nicorandil on these parameters may be through opening of K ATP channels that may oppose Ca 2+ -dependent acid secretion [4] and pepsin activity [28].…”

Effects of calcium channel blockers on gastric emptying and acid secretion of the rat in vivo

“…In the pylorus-ligated rat both verapamil and diltiazem inhibited the volume of gastric secretion and total acid output in a dosedependent manner. Although pepsin and acid secretion are usually affected by drugs in the same way (Kontureck, 1980;Esplugues et al, 1982), in this case pepsin secretion remained unaffected by calcium blockers suggesting no significant involvement of Ca2" in the physiological secretion of this enzyme.…”

(R)-Alpha-Methylhistamine Inhibits Ethanol-lnduced Gastric Lesions in the Rat: Involvement of Histamine H₃ Receptors?

“…However, the involve ment of H| receptors seems unlikely, if we consider that the Hi agonist, 2-pyridylethylamine, promotes lesion for mation [19] and the Hi antagonist, tripelennamine, re duces the severity of gastric lesions [20], In contrast, H2 receptors have been shown to be responsible for the marked inhibition exerted by histamine and dimaprit against 0.6 N HCl-induced gastric lesions in the rat [20], even though both compounds, by increasing the dose, are reported to cause acute gastric lesions [19,21], The hista mine and dimaprit protective effect is completely antago nized by cimetidine and, being abolished by indomethacin pretreatment, has been causally related with the for mation of endogenous prostaglandins, via H2 receptors [20], In this respect, histamine and MHA appear to differ. FAM only partially reversed the MHA effect, indicating that the contribution of H2 receptors is limited and, in addition, the indomethacin pretreatment resulted in a similarly partial reduction of the MHA effect.…”