PITUITARY CELL-LINE GH(3) EXPRESSES 2 SOMATOSTATIN RECEPTOR SUBTYPES THAT INHIBIT ADENYLYL-CYCLASE - FUNCTIONAL EXPRESSION OF RAT SOMATOSTATIN RECEPTOR SUBTYPE-1 AND SUBTYPE-2 IN HUMAN EMBRYONIC KIDNEY 293-CELLS

Using a polymerase chain reaction approach, we have studied the expres sion of somatostatin receptor (SSTR) subtypes in the GH-3 rat pituitar y cell line, a well established in vitro model for the cellular effect s of somatostatin. We found that the previously identified SSTR1 and S STR2 are the major subtypes expressed in this cell line. No other SSTR subtype was detected by our analysis. Northern blots confirmed that b oth subtypes, but not SSTR3, are expressed in GH-3 cells. We studied t he functional expression of both SSTR subtypes by transfection of thei r cDNAs into human embryonic kidney 293 cells. We found that somatosta tin inhibited cAMP accumulation in human embryonic kidney 293 cells on ly when cells were transfected with either SSTR1 or SSTR2. This inhibi tion was blocked by treatment of the transfected cells with pertussis toxin, demonstrating that it is mediated by G proteins sensitive to th is toxin. In addition, we provide pharmacological evidence that the en dogenous SSTR2 subtype mediates inhibition of cAMP accumulation in int act GH-3 cells. Our results contradict previous reports that concluded that neither SSTR1 nor SSTR2 is involved in inhibition of adenylyl cy clase. The reasons for this apparent contradiction are discussed, We c onclude that both SSTR1 and SSTR2 are capable of coupling to pertussis toxin-sensitive G proteins to inhibit adenylyl cyclase.