Inhibitory effects of somatostatin on glucagon-like peptide-1-mediated acceleration of peristalsis in the rat proximal colon

Colonic motility is controlled by the enteric nervous system that is modulated not only by autonomic neurotransmitters but also by substances released from enteroendocrine cells. Glucagon-like peptide-1 (GLP-1) secreted from L cells accelerates peristalsis of the proximal colon, whereas somatostatin released from D cells inhibits GLP-1 secretion via the activation of somatostatin receptor subtype 5 (SST5). Here, effects of somatostatin on GLP-1-mediated acceleration of colonic peristalsis were investigated. Cannulated segments of rat proximal colon were serosally perfused with oxygenated physiological salt solution and luminally perfused with degassed solution. Colonic wall motion was imaged and converted into spatiotemporal maps. Distributions of somatostatin and SST5 receptors were assessed via immunohistochemistry. Intraluminal administration of somatostatin alone did not affect oro-aboral propagating peristaltic contractions, but prevented luminal-applied GLP-1 (30 nM)-induced acceleration of peristaltic waves. Somatostatin also prevented the prokinetic action of endogenous GLP-1 that was released upon the stimulation by luminal-applied short-chain fatty acids (SCFA, 3 mM) or lipopolysaccharide. In colonic segments that had been pretreated with selective SST5 receptor antagonist 1, a lower concentration of GLP-1 (10 nM) or SCFA (300 µM) became capable of accelerating peristaltic waves. GLP-1-positive epithelial cells coexpressed SST5 receptors, whereas GLP-1 receptor-positive epithelial cells and afferent neurons contained somatostatin. Thus, L cell-derived GLP-1 that accelerates colonic peristalsis may simultaneously stimulate D cells and afferents to release somatostatin that serves as a break on prokinetic actions of GLP-1 by activating SST5 receptors on L cells. This interplay between GLP-1 and somatostatin would prevent excessive colonic motility.NEW & NOTEWORTHY Somatostatin inhibited the prokinetic action of glucagon-like peptide-1 (GLP-1), short-chain fatty acids, and lipopolysaccharide. The inhibitory effect of somatostatin was mediated by the activation of somatostatin receptor subtype 5 that was expressed on L cells. Sources of somatostatin were D cells and intrinsic primary afferent neurons, both of which expressed GLP-1 receptors. Thus, colonic peristalsis may well be regulated by the functional interaction between excitatory GLP-1 and inhibitory somatostatin.