The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. http://http://dspace.unitus.it:80 2013-05-18T18:42:06Z 2013-05-18T18:42:06Z Ristori, Chiara Ferretti, Maria Enrica Pavan, Barbara Cervellati, Franco Casini, Giovanni Catalani, Elisabetta Dal Monte, Massimo Biondi, Carla http://hdl.handle.net/2067/1448 2011-06-06T16:17:24Z 2007-12-31T23:00:00Z

Title: Adenylyl cyclase/cAMP system involvement in the antiangiogenic effect of somatostatin in the retina. Results from transgenic mice. Authors: Ristori, Chiara; Ferretti, Maria Enrica; Pavan, Barbara; Cervellati, Franco; Casini, Giovanni; Catalani, Elisabetta; Dal Monte, Massimo; Biondi, Carla Abstract: Neoangiogenesis is a response to retinal hypoxia that is inhibited by somatostatin (SRIF) through its subtype 2 receptor (sst2). Using a mouse model of hypoxia-induced retinopathy, we investigated the possibility that inhibition of adenylyl cyclase (AC) is involved in SRIF anti-angiogenic actions. Hypoxia increased AC responsiveness in wild type (WT) retinas and in retinas lacking sst2, but not in sst2-overexpressing retinas. Hypoxia also altered AC isoform expression, but with different patterns depending on sst2 expression level. Among the nine AC isoforms, AC VII isoform mRNA and protein resulted the most affected. Indeed, in hypoxia AC VII expression was significantly enhanced in WT retinas and it was further increased in sst2-lacking retinas, but not in retinas overexpressing sst2. These data suggest an involvement of AC/cAMP in mediating both hypoxia-evoked retinal neoangiogenesis and SRIF protective actions. The AC VII isoform is a candidate to a main role in these mechanisms. Description: L'articolo è disponibile sul sito dell'editore http://www.springerlink.com/

2007-12-31T23:00:00Z Ristori, Chiara Cammalleri, Maurizio Martini, Davide Pavan, Barbara Casini, Giovanni Cervia, Davide Bagnoli, Paola http://hdl.handle.net/2067/1486 2011-06-27T12:10:19Z 2007-12-31T23:00:00Z

Title: The cyclooxygenase-2/prostaglandin E2 pathway is involved in the somatostatin-induced decrease of epileptiform bursting in the mouse hippocampus Authors: Ristori, Chiara; Cammalleri, Maurizio; Martini, Davide; Pavan, Barbara; Casini, Giovanni; Cervia, Davide; Bagnoli, Paola Abstract: The neuromodulatory peptide somatostatin-14 (SRIF) plays an important inhibitory role in epilepsy, but little is known on the signalling mechanisms coupled to this effect of SRIF. We have previously demonstrated that SRIF induces reduction of epileptiform bursting in a model of interictal-like activity in mouse hippocampal slices. In this same model, we investigated whether the cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) pathway is part of those signalling mechanisms mediating SRIF anti-epileptic actions. Both the expression of COX-2 (mRNA and protein) and the endogenous release of PGE2 increased in concomitance with epileptiform bursting. In particular, COX-2 protein increased in CA1/CA3 pyramidal layer and in the granular layer of the dentate gyrus. In addition, the selective inhibition of COX-2 by NS-398 markedly decreased endogenous PGE2 release induced by epileptiform bursting and the epileptiform bursting itself. Similar effects on epileptiform bursting were obtained with another COX-2 inhibitor, i.e., meloxicam. SRIF application counteracted the increase of both COX-2 expression and PGE2 release which occurred in concomitance with epileptiform bursting. Interestingly, SRIF and NS-398 comparably reduced epileptiform bursting in a non-additive manner and PGE2 abolished the inhibitory effect of SRIF on epileptiform bursting. These results demonstrate that: i) the COX-2/PGE2 pathway facilitates epileptiform bursting; and ii) SRIF exerts an anti-epileptic role by coupling to the COX-2/PGE2 pathway. In conclusion, we have identified a key set of signalling events that underlie anti-convulsant effects of SRIF in a mouse model of hippocampal bursting, thus providing useful data not only to identify alternative intervention points for the modulation of SRIF function, but also to exploit new chemical space for drug-like molecules. Description: L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com/

2007-12-31T23:00:00Z Ristori, Chiara Cammalleri, Maurizio Martini, Davide Pavan, Barbara Liu, Yanqiang Casini, Giovanni Dal Monte, Massimo Bagnoli, Paola http://hdl.handle.net/2067/1485 2011-06-28T14:05:00Z 2007-12-31T23:00:00Z

Title: Involvement of the cAMP-dependent pathway in the reduction of epileptiform bursting caused by somatostatin in the mouse hippocampus Authors: Ristori, Chiara; Cammalleri, Maurizio; Martini, Davide; Pavan, Barbara; Liu, Yanqiang; Casini, Giovanni; Dal Monte, Massimo; Bagnoli, Paola Abstract: The cAMP pathway is major signal transduction system involved in hippocampal neurotransmission. Recently, the peptide somatostatin-14 (SRIF) has emerged as a key signal that, by activating its receptors, inhibits epileptiform bursting in the mouse hippocampus. Little is known on transduction mechanisms which may mediate SRIF function in native cell/tissues. Using a well established model of epileptiform activity induced by Mg2+-free medium with 4-aminopyridine (0 Mg2+⁄4-AP) in mouse hippocampal slices, we demonstrated that PKA-related signaling is upregulated by hippocampal bursting and that treatment with SRIF normalizes this upregulation. We also demonstrated that the SRIF-induced inhibition of PKA impairs phosphorylation of the NMDA receptor subunit NR1. Extracellular recordings of the 0 Mg2+⁄4-AP-induced hippocampal discharge from the CA3 region demonstrated that treating slices with compounds which interfere with PKA activity prevent SRIF inhibition of epileptiform bursting. Our results suggest that SRIF modulation of hippocampal activity may involve PKA-related signaling. Description: L'articolo è disponibile sul sito dell'editore http://www.springerlink.com

2007-12-31T23:00:00Z Cammalleri, Maurizio Cervia, Davide Dal Monte, Massimo Martini, Davide Langenegger, Daniel Fehlmann, Dominique Feuerbach, Dominik Pavan, Barbara Hoyer, Daniel Bagnoli, Paola http://hdl.handle.net/2067/1460 2011-06-28T10:33:18Z 2005-12-31T23:00:00Z

Title: Compensatory changes in the hippocampus of somatostatin knockout mice: upregulation of somatostatin receptor 2 and its function in the control of bursting activity and synaptic transmission Authors: Cammalleri, Maurizio; Cervia, Davide; Dal Monte, Massimo; Martini, Davide; Langenegger, Daniel; Fehlmann, Dominique; Feuerbach, Dominik; Pavan, Barbara; Hoyer, Daniel; Bagnoli, Paola Abstract: Somatostatin-14 (SRIF) colocalizes with GABA in the hippocampus and regulates neuronal excitability. A role of SRIF in the control of seizures has been proposed although its exact contribution requires some clarification. In particular, SRIF knock out (KO) mice do not exhibit spontaneous seizures, indicating that compensatory changes may occur in KO. In the KO hippocampus, we examined whether specific SRIF receptors and/or the cognate peptide cortistatin-14 (CST) compensate for SRIF’s absence. We found increased levels of both sst2 receptors (sst2) and CST and we explored the functional consequences of sst2 compensation on bursting activity and synaptic responses in hippocampal slices. Bursting was decreased by SRIF in wild type (WT) mice, but it was not affected by either CST or sst2 agonist and antagonist. sst4 agonist increased bursting frequency in either WT or KO. In WT, but not in KO, its effects were blocked by agonizing or antagonizing sst2, suggesting that sst2 and sst4 are functionally coupled in the WT hippocampus. Bursting was reduced in KO as compared to WT and was increased upon application of sst2 antagonist while SRIF, CST and sst2 agonist had no effect. At the synaptic level, we observed that in WT, SRIF decreased excitatory postsynaptic potentials which were, in contrast, increased by sst2 antagonist in KO. We conclude that sst2 compensates for SRIF absence and that its upregulation is responsible for reduced bursting and decreased excitatory transmission in KO mice. We suggest that a critical density of sst2 is needed to control hippocampal activity. Description: L'articolo è disponibile sul sito dell'editore http://onlinelibrary.wiley.com/

2005-12-31T23:00:00Z 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 Cervia, Davide Fiorini, Sara Pavan, Barbara Biondi, Carla Bagnoli, Paola http://hdl.handle.net/2067/1432 2011-06-25T10:59:16Z 2001-12-31T23:00:00Z

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/

2001-12-31T23:00:00Z Pavan, Barbara Fiorini, Sara Dal Monte, Massimo Lunghi, Laura Biondi, Carla Bagnoli, Paola Cervia, Davide http://hdl.handle.net/2067/1453 2011-06-27T09:30:01Z 2003-12-31T23:00:00Z

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/

2003-12-31T23:00:00Z