MULTIPLE EFFECTOR COUPLING OF SOMATOSTATIN RECEPTOR SUBTYPE SSTR1

The signal transduction pathways of a cloned human somatostatin recept or subtype, SSTR1, have been investigated in CHO cells stably expressi ng this receptor. In SSTR1-expressing CHO cells, somatostatin-14 inhib its forskolin-stimulated cAMP formation in a dose-dependent manner wit h an ED(50) of 1.0 x 10(-9) M. Somatostatin-14 also stimulates inosito l 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 c yclase and stimulatory action on inositol 1,4,5-trisphosphate formatio n are both blocked by pertussis toxin, indicating that these effects o f SSTR1 are mediated by pertussis toxin-sensitive G protein(s). Antise rum 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 coup les SSTR1 to adenylylcyclase. These results demonstrate that SSTR1 can be coupled to different signaling pathways to exert multiple biologic al effects, one of which is mediated by Gi alpha 3. (C) 1994 Academic Press, Inc.