THE SOMATOSTATIN RECEPTOR SUBTYPE ON RAT ENTEROCHROMAFFIN-LIKE CELLS

Background/Aims: Gastric enterochromaffinlike (ECL) cells play an impo rtant role in peripheral regulation of acid secretion. This study inve stigated the somatostatin receptor subtype on ECL cells. Methods: ECL cells were isolated from rat fundic mucosa to a purity of 90%-95% by c ombining enzymatic digestion, elutriation, density gradient centrifuga tion, and culture. Results: Polymerase chain reaction performed with t emplates from an ECL cell complementary DNA library and primers specif ic to each of the five known somatostatin receptor subtypes showed tha t the somatostatin receptor type 2 was significantly enriched in ECL c omplementary DNA. Single cell videoimaging of highly purified ECL cell s in culture showed that only the somatostatin receptor type 2 selecti ve agonist, DC 32-87, inhibited the gastrin-induced calcium signal at 10(-11) mol/L. The type 3 and type 4 selective agonists, DC 25-12 and DC 32-92, and also somatostatin 14 required 100-1000 times higher conc entrations (10(-8) mol/L). The somatostatin receptor type 2 analogue a lso inhibited gastrin-stimulated histamine release with a 50% inhibito ry concentration (IC50 value of 2 x 10(-12) mol/L, whereas somatostati n 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10( -9) mol/L. Conclusions: The predominant somatostatin receptors on rat gastric ECL cells are of the somatostatin receptor 2 subtype; they inh ibit histamine secretion by interfering with the gastrin-induced calci um signal.