Central somatostatin diminished inhibitory action of central CGRP on pancreatic basal secretion in conscious rats

We examined whether central somatostatin prevents an inhibitory effect of central calcitonin-gene related peptide (CGRP) on pancreatic secretion in conscious male Wistar rats (330-330 g). Rats were prepared with separate cannulas for draining bile and pancreatic juice and with a duodenal cannula and an extrajugular vein cannula. In addition, another cannula was stereotactically implanted into the left lateral cerebral ventricle. Rats were placed in restraint cages and experiments were conducted 4 days after the operation without anesthesia. An injection of CGRP (0.1, 1.0 nmol/10 microl) into the left lateral cerebral ventricle (i.c.v.) inhibited pancreatic secretion dose-dependently. To confirm the inhibitory effect of CGRP (i.c.v.) was mediated via sympathetic nerves, phentolamine was injected intravenously (i.v.) bolus (0.5 mg kg(-1)) 0.5-h before CGRP (i.c.v.), followed by continuous infusion of 0.2 mg kg(-1) h(-1). Phentolamine (i.v.) reversed the inhibition produced by CGRP (i.c.v.). An injection of 4 nmol/10 microl somatostatin (i.c.v.) 5 min prior to CGRP injection diminished the inhibitory effect of CGRP (i.c.v.). It is concluded that centrally administered somatostatin diminished the inhibitory action of CGRP (i.c.v.) on pancreatic secretion, probably via inhibiting autonomic (sympathetic) nerve excitation at the central site.