http://http://dspace.unitus.it:80 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. Fri, 24 May 2013 17:13:29 GMT 2013-05-24T17:13:29Z http://hdl.handle.net/2067/1432 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 Abstract: 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. Description: L'articolo è disponibile sul sito dell'editore http://www.springerlink.com/ Mon, 31 Dec 2001 23:00:00 GMT http://hdl.handle.net/2067/1432 2001-12-31T23:00:00Z http://hdl.handle.net/2067/1453 Title: Somatostatin coupling to adenylyl cyclase activity in the mouse retina Authors: Pavan, Barbara; Fiorini, Sara; Dal Monte, Massimo; Lunghi, Laura; Biondi, Carla; Bagnoli, Paola; Cervia, Davide Abstract: The peptide somatostatin-14 (SRIF) acts in the mammalian retina through its distinct receptors (sst1-5). Scarce information is available on SRIF function in the retina, including the elucidation of transduction pathways mediating SRIF action. We have investigated SRIF and SRIF receptor modulation of adenylyl cyclase (AC) activity in both wild type (WT) retinas and sst1 or sst2 knock-out (KO) retinas which are known to over-express sst2 or sst1 receptors, respectively. In WT retinas, application of SRIF compounds does not affect forskolin-stimulated AC activity. In contrast, activation of sst1 or sst2 receptors inhibits AC in the presence of sst2 or sst1 receptor antagonists, respectively. Results from sst1 KO retinas demonstrate that either SRIF or octreotide, pertussis toxin-dependently inhibit AC activity. In contrast, in sst2 KO retinas, neither SRIF nor CH-275, an sst1 receptor agonist, are found to influence AC activity. As revealed by immunoblotting experiments, in sst1 KO retinas, levels of Goα proteins are 60% higher than in WT retinas and this increase in Goα protein levels is concomitant with an increase in sst2A receptor expression. We conclude that interactions between sst1 and sst2 receptors may prevent SRIF effects on AC activity. In addition, we suggest that the density of sst2 receptors and/or Goα proteins may represent the rate-limiting factor for the sst2 receptor-mediated inhibition of AC. Description: L'articolo è disponibile sul sito dell'editore http://www.springerlink.com/ Wed, 31 Dec 2003 23:00:00 GMT http://hdl.handle.net/2067/1453 2003-12-31T23:00:00Z