Human circular colonic smooth muscle cells possess active somatostatin receptors

Background & Aims. Somatostatin alters in vivo colonic motility in differen t species including humans. Few data are available on a cellular basis that could explain the effects of somatostatin on human colon motility. To addr ess these issues we studied the effects of somatostatin on isolated human c ircular colonic smooth muscle cells to establish whether its actions are di rectly or neurally mediated Methods, Circular smooth muscle cells were prepared by enzymatic digestion from surgical specimens of human colon (Sigma) and resuspended in HEPES buf fer containing protease inhibitors. Results, Cholecystokinin (1 nM), carbachol (30 nM) and KCI (20 mM) each cau sed a contraction of 17%, 16.5% and 15%, respectively 1 mu M of either soma tostarin-14 somatostatin-28 or SMS 201-995 alone were able to produce a con traction of 5.1 %, 5.7%, and 6.8%, respectively. When smooth muscle cells w ere preincubated with each of the above-mentioned somatostatin analogs, cho lecystokinin-mediated contraction was dose-dependently inhibited only in th e presence of antiproteases. The half-maximal effective concentration (EC50 ) for somatostatin-14, somatostatin-28 and SMS 201-995 were similar (3.5, 5 .6 3.2 nM, respectively). Conclusions, Somatostatin acts directly on human circular colonic smooth mu scle cells through specific somatostatin receptors. SMS 201-995, a somatost atin receptor subtype-2 preferring analogue, shows a high affinity in inhib iting cholecysrokinin-mediated contraction, suggesting the presence of soma tostatin receptor subtype-2 on human circular colonic smooth muscle cells.