The observation that somatostatin and its analogue octreotide inhibit the release of various peptide hormones and transmitters from neuroendocrine tumors has stimulated interest in the signal transduction pathway mediated by these compounds. Using the whole cell mode of the patch-clamp technique, we investigated the inhibitory effects of somatostatin and octreotide on voltage-dependent calcium channels (VDCC) in isolated human neuroendocrine tumor cells of the gut. Both peptides dose dependently and reversibly inhibited VDCC. Somatostatin (100 nM) reduced the current amplitude by 38 +/- 19% and 100 nM octreotide by 35 +/- 14%. Human neuroendocrine gut tumor cells preferentially express dihydropyridine-sensitive L-type VDCC, since most of the inward current was sensitive to the dihydropyridine isradipine. The inhibitory effects of isradipine and octreotide were not additive and octreotide had little effect on the isradipine-resistant inward current. Since octrotide selectively binds to the somatostatin receptor subtypes 2 and 5, these results suggest that inhibition of calcium-dependent hormone release by somatostatin from human neuroendocrine gut cells appears to involve somatostatin receptor subtypes 2 and 5, as well as dihydropyridine-sensitive L-type VDCC.
