EFFECTS OF CLONIDINE ON GASTRIC-ACID SECRETION IN THE RAT

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (1) , 121-126
Abstract
The effect of clonidine on gastric acid secretion was studied in the pylorus ligated stomach (Shay test) and in the perfused stomach of the rat. Clonidine produced biphasic (inhibitory and stimulatory) effects on gastric acid secretion. In the Shay test, clonidine produced only an inhibitory effect on spontaneous gastric acid secretion in a dose-dependent manner (ED50 = 0.042 mg/kg, intraduodenal administration). In the perfused stomach, clonidine in a dose range of 0.625-5 mg/kg i.p. slightly increased acid secretion. The secretion, induced by 5 mg/kg of clonidine, was antagonized by cimetidine (10 mg/kg i.p.) but was not affected by phentolamine. Clonidine, 1.25 mg/kg i.p., a dose which had only a slight stimulatory effect, enhanced histamine- and bethanechol-induced secretion. The enhancement of bethanechol-induced secretion was blocked by pretreatment with cimetidine, suggesting histamine H2 receptor stimulation by clonidine. After i.p. (1.25 mg/kg) or intracerebroventricular (i.c.v., 20 and 40 .mu.g/kg) administration, clonidine antagonized 2-deoxy-D-glucose-induced acid secretion. Clonidine also inhibited secretion induced by vagal stimulation in anesthetized, vagi-sectioned rats. Clonidine evidently had both central and peripheral sites of action. The inhibitory effect on secretion induced by vagal stimulation was blocked by phentolamine (.alpha.1, and .alpha.2 adrenergic receptor blocker) but not by labetalol (which blocks .alpha.1 but not .alpha.2 receptors). The inhibitory effect of clonidine may be due to its effect on presynaptic .alpha.2 adrenergic receptors located on the postganglionic vagal fibers to the stomach. These data suggest that clonidine inhibited gastric acid secretion by both a central and a peripheral mechanism. As the dose was increased, clonidine also stimulated acid secretion by a stimulation of histamine H2 receptors.

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