Somatostatin (SRIF) modulates distinct signaling pathways in rat pituitary tumor cells; negative coupling of SRIF receptor subtypes 1 and 2 to arachidonic acid release

The somatotropin release-inhibiting factor somatostatin-14 (SRIF) is known to activate distinct receptor subtypes (sst(1-5)). In rat pituitary tumor cells (GC cells), sst(2) but not sst(1) receptors mediate the SRIF-induced inhibition of intracellular concentration of Ca2+ ([Ca2+](i)) and are negatively coupled to cAMP-dependent pathways. In the present study, transduction mechanisms coupling distinct SRIF receptors to their specific functional role were investigated with the use of both SRIF agonists with well-known affinity at individual SRIF receptors and the sst(2) receptor antagonist L-Tyr(8) isomer of Cyanamid 154806 (CYN-154806). Our results demonstrate that sst(1) and sst(2) receptors are coupled to distinct signaling pathways in GC cells. In particular, sst(2) receptors are negatively coupled to the cAMP-dependent pathway and this pathway is partially responsible for the sst(2) receptor-mediated inhibition of [Ca2+](i). In addition, sst(1) and sst(2) receptors are both coupled to a decrease of arachidonic acid (AA) release with an efficacy similar to that of SRIF, suggesting that SRIF reduces AA release through either a partial activation of both receptors or the activation of one at a time. This finding is important given the well-accepted role for phospholipase A(2) (PLA(2)) as a positive signaling component in transduction pathways of SRIF receptors. sst(1) and sst(2) receptor negative coupling to PLA(2)/AA pathways does not seem to be implicated in the SRIF-induced inhibition of [Ca2+](i). The possible role for the SRIF-mediated inhibition of AA release in GC cell function remains to be elucidated.