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Somatostatin coupling to adenylyl cyclase activity in the mouse retina

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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 the sst2 receptor preferring agonist 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.

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Acknowledgements

We wish to thank A. Gazzano for assistance with KO mouse colonies and G. Bresciani for animal care. We are grateful to D. Richter (University of Hamburg, Germany) and to J.P. Allen (Babraham Institute, Cambridge, UK) for providing us with the sst1 or sst2 KO mice respectively. We wish to thank D. Hoyer (Novartis Pharma, Basel, Switzerland) for providing us with octreotide, SRA880 and CYN. We are also grateful to G. Casini (University of Tuscia, Viterbo, Italy) for revising the manuscript. This work was supported by the Italian Board of Education (F06/FISR to PB and CB) and the European Community (QLG3-1999-00908 to PB).

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Authors and Affiliations

  1. Dipartimento di Biologia, Sez. di Fisiologia Generale, Università di Ferrara, 44100, Ferrara, Italy

    Barbara Pavan, Sara Fiorini, Laura Lunghi & Carla Biondi

  2. Dipartimento di Fisiologia e Biochimica “G. Moruzzi”, Università di Pisa, 56127, Pisa, Italy

    Massimo Dal Monte, Paola Bagnoli & Davide Cervia

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  1. Barbara Pavan
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  2. Sara Fiorini
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  3. Massimo Dal Monte
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  4. Laura Lunghi
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  5. Carla Biondi
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  6. Paola Bagnoli
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  7. Davide Cervia
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Correspondence to Davide Cervia.

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Pavan, B., Fiorini, S., Dal Monte, M. et al. Somatostatin coupling to adenylyl cyclase activity in the mouse retina. Naunyn-Schmiedeberg's Arch Pharmacol 370, 91–98 (2004). https://doi.org/10.1007/s00210-004-0950-5

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