Somatostatin receptors (sst2) are coupled to Go and modulate GTPase activity in the rabbit retina

Journal of Neurochemistry - Tập 84 Số 4 - Trang 625-632 - 2003
Anna Vasilaki1, Zafiroula Georgoussi2, Kyriaki Thermos3
1Laboratory of Pharmacology, Department of Basic Science, Faculty of Medicine, University of Crete, Heraklion, Crete 71110, Greece.
2Institute of Biology, N.C.S.R. ‘‘Demokritos’’, Athens, Greece
3Laboratory of Pharmacology, University of Crete, Faculty of Medicine, Heraklion, Crete

Tóm tắt

AbstractThe role of somatostatin and its mechanism of action in the retina remains an important target for investigation. Biochemical and pharmacological studies were engaged to characterize the somatostatin receptors in the rabbit retina, and their coupling to G‐proteins. The ability of selective ligands to inhibit [125I]Tyr11‐somatostatin‐14 binding to rabbit retinal membranes was examined. The sst2 analogues SMS201–995, MK678, and BIM23014, displayed IC50 values of 0.28 ± 0.12, 0.04 ± 0.01 and 1.57 ± 0.39 nm, respectively. The sst1 analogue CH275 moderately displaced the [125I]Tyr11‐somatostatin‐14 binding, while selective analogues for sst3, sst4 and sst5 had minimal effect. Immunoblotting and/or immunohistochemistry studies revealed the presence of the pertussis toxin sensitive Gi1/2, and Go proteins, as well as Gs. Somatostatin‐14 and MK678 stimulated GTPase activity in a concentration‐dependent manner with EC50 values of 42.8 ± 16.8 and 70.0 ± 16.5 nm, respectively, thus supporting the functional coupling between the receptor and the G‐proteins. CH275 stimulated the GTPase activity moderately, in agreement with its binding profile. The antisera raised against Goα and Gi1/2α inhibited the somatostatin‐induced high‐affinity GTPase activity, but only anti‐Goα inhibited the MK678 stimulation of the enzyme. These results suggest that somatostatin mediates its actions in the rabbit retina by interacting mainly with sst2 receptors that couple to Goα.

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Journal of Neurochemistry

Tập 84 Số 4

625-632

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