INHIBITION OF L-TYPE CALCIUM CHANNELS BY OCTREOTIDE IN ISOLATED HUMANNEUROENDOCRINE TUMOR-CELLS OF THE GUT

The observation that somatostatin and its analogue octreotide inhibit the release of various peptide hormones and transmitters from neuroend ocrine tumors has stimulated interest in the signal transduction pathw ay mediated by these compounds. Using the whole cell mode of the patch -clamp technique, we investigated the inhibitory effects of somatostat in and octreotide on voltage-dependent calcium channels (VDCC) in isol ated human neuroendocrine tumor cells of the gut. Both peptides dose d ependently and reversibly inhibited VDCC, Somatostatin (100 nM) reduce d the current amplitude by 38 +/- 19% and 100 nM octreotide by 35 +/- 14%. Human neuroendocrine gut tumor cells preferentially express dihyd ropyridine-sensitive L-type VDCC, since most of the inward current was sensitive to the dihydropyridine isradipine, The inhibitory effects o f isradipine and octreotide were not additive and octreotide had littl e effect on the isradipine-resistant inward current. Since octreotide 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-se nsitive L-type VDCC. (C) 1998 Academic Press.