Further support for the central origin of the gastric antisecretory properties of clonidine in conscious rats

Abstract

The effects of clonidine (CL) on interdigestive gastric acid secretion were studied in chronic gastric fistula rats and compared with those of St 91, a CL-like drug which does not cross the blood-brain barrier. CL induced a dose-dependent inhibition of gastric acid output when administered s.c. (ED 50 13.5 μg·kg −1), in the lateral ventricle of the brain (ED 50 5.80 μg·kg −1) or in the cisterna magna (ED 50 0.49 μg·kg −1). St 91 and several α-adrenergic antagonists administered subcutaneously also inhibited gastric acid secretion dose dependently. Decreasing activities were prazosin > St 91 > phentolamine > yohimbine > piperoxan; phenoxybenzamine was a poor inhibitor. The anti-secretory properties of CL on basal secretion were antagonized by yohimbine and piperoxan. Other drugs either did not antagonize (phentolamine) or potentiated (phenoxybenzamine, prazosin) the CL effect, while yohimbine and phenoxybenzamine potentiated the response to St. 91. CL had no activity on methacholine while it drastically inhibited 2-DG-, histamine- and pentagastrin-stimulated gastric secretion. The inhibitory activity of CL on histamine stimulation was significantly decreased by yohimbine but not by phentolamine. These results confirm that the CL inhibition of the gastric acid secretion in unanesthetized rats is mediated at least partly through the stimulation of α 2-adrenergic receptors. Most of the data favour a major role of the CNS in the antisecretory activity of CL and suggest the possibility that most of the receptors involved are located in the medulla oblongata.