Rat somatostatin sst2(a) and sst2(b) receptor isoforms mediate opposite effects on cell proliferation

We have investigated the actions of somatostatin (SRIF) and angiopeptin on cell proliferation of CHO-K1 cells expressing the recently cloned rat sst(2(b)) receptor (CHOsst(2(b))) and compared these to their effects in cells expressing the sst(2(a)) receptor (CHOsst(2(a))). In contrast to the sst(2(a)) receptor, the sst(2(b)) receptor did not mediate inhibition of bFGF (10 ng ml(-1))-stimulated re-growth and cell proliferation. Rather, SRIF (0.1-1000 nM) and angiopeptin (0.1-1000 nM) stimulated basal regrowth and proliferation of CHOsst(2(b)) cells in a concentration-dependent manner (estimated pEC(50) values of 7.8 and 7.9, respectively). The opposite effects of SRIF on cell proliferation mediated through the two sst(2) receptor isoforms were both abolished by 18 h pre-treatment with pertussis toxin. The proliferative effect via the sst(2(b)) receptor was also abolished by the tyrosine kinase inhibitor, genistein. In conclusion, the present study shows that the rat sst(2(a)) and sst(2(b)) receptor splice variants mediate opposite effects on cell proliferation.