MULTIPLE EFFECTOR COUPLING OF SOMATOSTATIN RECEPTOR SUBTYPE SSTR1

The signal transduction pathways of a cloned human somatostatin receptor subtype, SSTR1, have been investigated in CHO cells stably expressing this receptor. In SSTR1-expressing CHO cells, somatostatin-14 inhibits forskolin-stimulated cAMP formation in a dose-dependent manner with an ED(50) of 1.0 x 10(-9) M. Somatostatin-14 also stimulates inositol 1,4,5-trisphosphate formation in a dose-dependent manner with an ED(50) of 4.0 x 10(-8) M. Somatostatin-14 inhibitory action on adenylyl cyclase and stimulatory action on inositol 1,4,5-trisphosphate formation are both blocked by pertussis toxin, indicating that these effects of SSTR1 are mediated by pertussis toxin-sensitive G protein(s). Antiserum against Gi alpha 3 blocked the inhibitory effects of somatostatin-14 on forskolin-stimulated adenylyl cyclase, but antiserum against Gi alpha 1/Gi alpha 2 did not, indicating that Gi alpha 3 dominantly couples SSTR1 to adenylylcyclase. These results demonstrate that SSTR1 can be coupled to different signaling pathways to exert multiple biological effects, one of which is mediated by Gi alpha 3. (C) 1994 Academic Press, Inc.