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

Abstract.

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), sst₂ but not sst₁ 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 sst₂ receptor antagonist L-Tyr⁸ isomer of Cyanamid 154806 (CYN-154806). Our results demonstrate that sst₁ and sst₂ receptors are coupled to distinct signaling pathways in GC cells. In particular, sst₂ receptors are negatively coupled to the cAMP-dependent pathway and this pathway is partially responsible for the sst₂ receptor-mediated inhibition of [Ca²⁺]_i. In addition, sst₁ and sst₂ 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 A₂ (PLA₂) as a positive signaling component in transduction pathways of SRIF receptors. sst₁ and sst₂ receptor negative coupling to PLA₂/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.