THE SOMATOSTATIN RECEPTORS SSTR1 AND SSTR2 ARE COUPLED TO INHIBITION OF ADENYLYL-CYCLASE IN CHINESE-HAMSTER OVARY CELLS VIA PERTUSSIS-TOXIN-SENSITIVE PATHWAYS

Somatostatin exerts multiple effects throughout the body by binding to specific somatostatin receptors. Two classes of somatostatin receptor s, SRIF1 and SRIF2, have been distinguished biochemically and pharmaco logically. Two cDNAs have been recently isolated that encode somatosta tin receptors 1 and 2 (SSTR1 and SSTR2, respectively). The pharmacolog ical characteristics of receptors expressing these cDNAs resemble thos e of the SRIF2 and SRIF1 classes of somatostatin receptors, respective ly. We stably expressed the rat homologs of both receptors in Chinese hamster ovary (CHO) cells (type K1). These transfected cell lines reco gnized the endogenous ligands SS14 and SS28 with high affinity, wherea s the synthetic analog MK678 identified only SSTR2. In preparations of CHO-SSTR1 or CHO-SSTR2 cells, SS14 and SS28 inhibited forskolin-stimu lated adenylyl cyclase activity by approximately 35%, with ED(50) valu es in the nanomolar range. The adenylyl cyclase inhibition was depende nt upon the guanine nucleotide GTP and could be ablated with pertussis toxin preincubation. The present data indicate that SSTR1 and SSTR2 a re coupled to inhibition of adenylyl cyclase via pertussis toxin-sensi tive G-proteins.