The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. http://http://dspace.unitus.it:80 2013-05-23T16:20:04Z 2013-05-23T16:20:04Z Dal Monte, Massimo Ristori, Chiara Videau, Catherine Loudes, Catherine Martini, Davide Casini, Giovanni Epelbaum, Jacques Bagnoli, Paola http://hdl.handle.net/2067/1429 2011-06-28T10:47:12Z 2009-12-31T23:00:00Z

Title: Expression, localization and functional coupling of the somatostatin receptor subtype 2 in a mouse model of oxygen-induced retinopathy Authors: Dal Monte, Massimo; Ristori, Chiara; Videau, Catherine; Loudes, Catherine; Martini, Davide; Casini, Giovanni; Epelbaum, Jacques; Bagnoli, Paola Abstract: PURPOSE. In the mouse model of oxygen-induced retinopathy (OIR) somatostatin (SRIF) acting at the SRIF receptor subtype 2 (sst2) inhibits angiogenic responses to hypoxia through a downregulation of vascular endothelial growth factor. Information on the sites where SRIF-sst2 interactions take place is lacking, and downstream effectors mediating SRIF-sst2 antiangiogenic actions are unknown. METHODS. In the OIR model, retinal expression of SRIF was evaluated with RT-PCR and RIA. The bindings of [125I]LTT-SRIF-28 and [125I]Tyr3-octreotide were measured in coronal sections of the eye. With Western blot we evaluated the levels of sst2A as well as the expression and the activity of the Signal Transducer and Activator of Transcription (STAT)3. The analysis of STAT3 was performed in hypoxic mice treated with the sst2 agonist octreotide or with the sst2 antagonist D-Tyr8 cyanamid 154806 (CYN). Retinal localization of sst2A was assessed by single and double immunohistochemistry with an endothelial cell marker. RESULTS. In the hypoxic retina, both SRIF and sst2 levels as well as [125I]Tyr3-octreotide binding were downregulated. In addition, sst2A immunostaining was decreased in the neuroretina, but was increased in capillaries. Hypoxia increased both expression and activity of STAT3. This increase was inhibited by octreotide, while was strengthened by CYN. CONCLUSIONS. These data suggest that i. sst2 expressed by capillaries may be responsible of the antiangiogenic effects of SRIF and ii. downstream effectors in this action include the transcription factor STAT3. These results support the possibility of using sst2- selective ligands in the treatment of proliferative retinopathies and indicate STAT3 as an additional target for novel therapeutic approach. Description: L'articolo è disponibile sul sito dell'editore http://www.arvo.org/eweb/StartPage.aspx?Site=arvo2

2009-12-31T23:00:00Z Dal Monte, Massimo Petrucci, Cristina Vasilaki, Anna Cervia, Davide Grouselle, Dominique Epelbaum, Jacques Kreienkamp, Hans-Jurgen Richter, Dietmar Hoyer, Daniel Bagnoli, Paola http://hdl.handle.net/2067/1449 2011-06-28T10:54:54Z 2002-12-31T23:00:00Z

Title: Genetic deletion of somatostatin receptor 1 alters somatostatinergic transmission in the mouse retina Authors: Dal Monte, Massimo; Petrucci, Cristina; Vasilaki, Anna; Cervia, Davide; Grouselle, Dominique; Epelbaum, Jacques; Kreienkamp, Hans-Jurgen; Richter, Dietmar; Hoyer, Daniel; Bagnoli, Paola Abstract: In the mammalian retina, sparse amacrine cells contain somatostatin-14 (SRIF) which acts at multiple levels of neuronal circuitry through distinct SRIF receptors (sst1-5). Among them, the sst1 receptor has been localized to SRIF-containing amacrine cells in the rat and rabbit retina. Little is known about sst1 receptor localization and function in the mouse retina. We have addressed this question in the retina of mice with deletion of sst1 receptors (sst1 KO mice). In the retina of wild type (WT) mice, sst1 receptors are localized to SRIF-containing amacrine cells whereas in the retina of sst1 KO mice, sst1 receptors are absent. sst1 receptor loss causes a significant increase in retinal levels of SRIF whereas it does not affect SRIF messenger RNA indicating that sst1 receptors play a role in limiting retinal SRIF at the post-transcriptional level. As another consequence of sst1 receptor loss, levels of expression of sst2 receptors are significantly higher than in control retinas. Together, these findings provide the first demonstration of prominent compensatory regulation in the mouse retina as a consequence of a distinct SRIF receptor deletion. The fact that in the absence of the sst1 receptor, retinal SRIF increases in concomitance with an increase in sst2 receptors suggests that SRIF may regulate sst2 receptor expression and that this regulatory process is controlled upstream by the sst1 receptor. This finding can be important in the design of drugs affecting SRIF function, not only in the retina, but also elsewhere in the brain. Description: L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com/

2002-12-31T23:00:00Z Cervia, Davide Petrucci, Cristina Bluet-Pajot, Marie Thérèse Epelbaum, Jacques Bagnoli, Paola http://hdl.handle.net/2067/1441 2011-06-28T12:50:21Z 2001-12-31T23:00:00Z

Title: Inhibitory control of growth hormone secretion by somatostatin in rat pituitary GC cells: sst2 but not sst1 receptors are coupled to an inhibition of single-cell intracellular free calcium concentrations Authors: Cervia, Davide; Petrucci, Cristina; Bluet-Pajot, Marie Thérèse; Epelbaum, Jacques; Bagnoli, Paola Abstract: Rat pituitary tumor cells (GC cells) exhibit spontaneous oscillations of intracellular free calcium concentration ([Ca2+]i) that allow a continuous release of growth hormone (GH). Of the SRIH receptor subtypes (sst receptors) mediating SRIH action, sst1 and sst2 receptors are highly expressed by GC cell membranes. In the present study, the effects of sst1 or sst2 receptor activation on single-cell [Ca2+]i were investigated in GC cells by confocal fluorescence microscopy. In addition, the effects of sst1 or sst2 receptor activation on GH secretion were also studied. Our results demonstrate that SRIH decreases [Ca2+]i baseline and almost completely blocks Ca2+ transients through the activation of sst2 but not of sst1 receptors. In contrast, SRIH effectively inhibits GH secretion through the activation of both sst1 and sst2 receptors. Blocking Ca2+ transients is less efficient than SRIH to inhibit GH release. The cyclic octapeptide, CYN-154806, antagonizes sst2 receptors at [Ca2+]i since it abolishes the sst2 receptor-mediated inhibition of [Ca2+]i without affecting single-cell Ca2+ signals. Unexpectedly, CYN-154806 alone potently inhibits GH secretion through the involvement of pertussis toxin-sensitive G proteins. In conclusion, the present results demonstrate that SRIH inhibition of GH release in GC cells involves mechanisms either dependent or independent on SRIH modulation of [Ca2+]i. The implications of CYN-154806 inhibition of GH secretion are discussed. Description: L'articolo è disponibile sul sito dell'editore http://www.karger.com

2001-12-31T23:00:00Z Cervia, Davide Zizzari, P. Pavan, Barbara Schuepbach, Edi Langenegger, Daniel Hoyer, Daniel Biondi, Carla Epelbaum, Jacques Bagnoli, Paola http://hdl.handle.net/2067/1443 2011-06-28T09:56:24Z 2002-12-31T23:00:00Z

Title: Biological activity of somatostatin receptors in GC rat tumour somatotrophs: evidence with sst1-sst5 receptor-selective nonpeptidyl agonists Authors: Cervia, Davide; Zizzari, P.; Pavan, Barbara; Schuepbach, Edi; Langenegger, Daniel; Hoyer, Daniel; Biondi, Carla; Epelbaum, Jacques; Bagnoli, Paola Abstract: The physiological actions of somatostatin-14 (SRIF) receptor subtypes (sst1-sst5), which are endogenously expressed in GC cells, have not yet been elucidated, although there is evidence that sst2 receptors are negatively coupled to cytosolic free Ca2+ concentration ([Ca2+]i) and cAMP accumulation. In addition, both sst1 and sst2 receptors are negatively coupled to growth hormone (GH) secretion in GC cells. Here we report on studies concerning the expression, the pharmacology and the functional role of native SRIF receptors in GC cells with the use of five nonpeptidyl agonists, highly selective for each of the SRIF receptors. Radioligand binding studies show that sst2 and sst5 receptors are present at different relative densities, while the presence of sst3 and sst4 receptors appears to be negligible. The absence of sst1 receptor binding was unexpected in view of sst1 receptor functional effects on GH secretion. This suggests very efficient receptor-effector coupling of a low density population of sst1 receptors. Functionally, only sst2 receptors are coupled to the inhibition of [Ca2+]i and cAMP accumulation and the selective activation of sst5 receptors facilitates the stimulation of adenylyl cyclase activity through Gi/o proteins. This effect was not observed when sst2 and sst5 receptors were simultaneously activated, suggesting that there is a functional interaction between sst2 and sst5 receptors. In addition, sst1, sst2 and sst5 receptor activation inhibits GH release, further indicating that SRIF can modulate GH secretion in GC cells through mechanisms both dependent and independent on [Ca2+]i and cAMP-dependent pathways. The present data suggest SRIF-mediated functional effects in GC cells to be very diverse and provide compelling arguments to propose that multiple native SRIF receptors expressed in the same cells are not simply redundant, but contribute to marked signalling diversity. Description: L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com/

2002-12-31T23:00:00Z