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Title: Somatostatin (SRIF) modulates distinct signaling pathways in rat pituitary tumor cells. Negative coupling of SRIF receptor subtypes 1 and 2 to arachidonic acid release
Authors: Cervia, Davide
Fiorini, Sara
Pavan, Barbara
Biondi, Carla
Bagnoli, Paola
Keywords: Peptide receptors;Agonists;Antagonist;Intracellular Ca2+;cAMP;PLA2/AA;Cell culture;Fluorimetry;Biochemical dosages;Somatostatin
Issue Date: 2002
Publisher: Springer Verlag
Source: Cervia, D. et al. 2002. Somatostatin (SRIF) modulates distinct signaling pathways in rat pituitary tumor cells; negative coupling of SRIF receptor subtypes 1 and 2 to arachidonic acid release. "Naunyn-Schmiedeberg's Archives of Pharmacology" 365(3):200-209
The somatotropin release inhibiting factor somatostatin-14 (SRIF) is known to activate distinct receptor subtypes (sst1-5). 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.
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ISSN: 0028-1298
DOI: 10.1007/s00210-001-0509-7
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