Stimulation of duodenal bicarbonate secretion in conscious rats by cerebral somatostatin-28. Role of neurohumoral pathways.

Abstract

The central nervous system effects of somatostatin-28 on proximal duodenal bicarbonate secretion were studied in freely moving rats. Cerebroventricular administration of somatostatin-28 (0.2-2.0 nmol) significantly stimulated duodenal bicarbonate secretion in a dose-dependent fashion. Somatostatin-28 was approximately twice as effective as somatostatin-14. Intravenous administration of somatostatin-28 or somatostatin-14 did not significantly alter the bicarbonate response. Ganglionic blockade with chlorisondamine and truncal vagotomy abolished the stimulatory effect of somatostatin-28 while bretylium, naloxone, indomethacin, and adrenalectomy did not. Furthermore, atropine methylnitrate significantly attenuated and the vasoactive intestinal peptide antagonist 4Cl-D-Phe6, Leu17-vasoactive intestinal peptide abolished the bicarbonate response produced by cerebroventricular somatostatin-28. In contrast, hypophysectomy and pretreatment with the vasopressin V1-receptor antagonist [1-deaminopenicillamine, 2-(0-methyl)Tyr, 8-Arg]-vasopressin significantly enhanced the bicarbonate response produced by cerebroventricular somatostatin-28. These findings indicate that somatostatin-28 acts within the central nervous system to stimulate duodenal bicarbonate secretion in freely moving rats via vagal efferents by release of vasoactive intestinal peptide and, in part, by a muscarinic pathway and not by catecholamine, opiate, or prostaglandin release.