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.