Molecular mechanisms of somatostatin's inhibition of hormone release: participation of voltage-gated calcium channels and G-proteins.
Somatostatin is known to inhibit hormone release from various neuroendocrine cells. In order to understand the mechanisms underlying somatostatin's action we performed patch-clamp experiments in GH3 pituitary, rMTC 44-2 thyroid and BON carcinoid cells. Calcium-mediated hormone release depended on the intracellular calcium concentration and thus on the calcium influx through voltage-gated calcium channels. In addition to inhibiting the cAMP-dependent secretory pathway, somatostatin reduced the calcium inward currents and thereby hormone release. The inhibition of voltage-gated calcium channels by somatostatin was mediated by "signal transducing" Go proteins. Thus, somatostatin's actions on hormone release involve both cAMP and intracellular calcium as second messengers. Patch-clamp experiments of voltage-gated calcium channels allow functional studies on the coupling of somatostatin receptors to cellular effector systems.
Scherübl
H
H
Department of Gastroenterology, University Hospital Steglitz, Free University of Berlin, Germany.
Hescheler
J
J
Riecken
E O
EO
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002276:Carcinoid Tumor; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D015282:Octreotide / Q000494:pharmacology*; D010911:Pituitary Neoplasms; D051381:Rats; D015398:Signal Transduction; D013004:Somatostatin / Q000494:pharmacology*; D013961:Thyroid Gland; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D013004:Somatostatin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D015282:Octreotide