Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats

Abstract

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-D-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect. somatostatin; pancreatic exocrine secretion; dorsal vagal complex; dorsal motor nucleus of the vagus nerve; somatostatin receptor antagonist; somatostatin receptor-2 agonist; cholecystokinin octapeptide; 2-deoxy-D-glucose

The islet-acinar axis of the pancreas: more than just insulin

“…These include central effects on the vagal and sympathetic pathways (106,118) or via somatostatin receptor 2 in the dorsal vagal complex (107). Peripheral effects include indirect actions through intrinsic peptidergic pancreatic neurons (132) or via an intrapancreatic cholinergic mechanism (92) whereby specific somatostatin receptors expressed on nerve terminals inhibit acetylcholine release (56).…”

Expression and localisation of somatostatin receptor subtypes sst1–sst5 in areas of the rat medulla oblongata involved in autonomic regulation

“…Groups of cholinergic vagal preganglionic neurones in the DVN and nucleus ambiguus, identified by ChAT immunoreactivity, were immunoreactive for sst2 A , sst2 B , sst4 and sst5. These neurones supply parasympathetic output to the heart, stomach and visceral organs, and studies in vivo and on slice preparations have shown that somatostatin affects visceral reflex activity by modulation of the activity of these neurones (Oomura and Mizuno, 1986;Yoneda et al, 1991;Wang et al, 1991a,b) in the case of output to the pancreas this was shown to involve sst2 receptors (Liao et al, 2007). The TH positive catecholamine neurones of the dorsomedial and ventrolateral medulla, implicated in the control of blood pressure (Colombari et al, 2001), mostly showed strong sst2 A immunoreactivity.…”

Inhibitory effect of somatostatin on insulin secretion is not mediated via the CNS

“…Casad & Adelman 1992, Zambre et al 1999, Strowski et al 2000, others have found that exogenous SST was ineffective in suppressing insulin or glucagon secretion from isolated mouse islets (Cejvan et al 2003, Hauge-Evans et al 2009). An analogous system has been reported in the exocrine pancreas, where exogenous SST did not inhibit enzyme secretion from isolated, arterially perfused pancreas, nor from acinar cells in vitro, but suppressed pancreatic enzyme release indirectly via binding to SSTR2 in the dorsal vagal complex (Liao et al 2007).…”

“…The effect of SST on the secretion of peptides from the exocrine pancreas and on intestinal uptake of water and electrolytes is mediated indirectly via the CNS (Primi & Bueno 1987, Li & Owyang 1993, Liao et al 2007) and other islet hormones have similarly been shown to convey their effects indirectly via the CNS in addition to their direct action on target tissues. For example, insulin acts indirectly via insulin receptors expressed on the ventromedial hypothalamus to modulate peripheral glucose homoeostasis in addition to its direct action on target tissues (Diggs-Andrews et al 2010, Paranjape et al 2010.…”