Inhibition of L-Type Calcium Channels by Octreotide in Isolated Human Neuroendocrine Tumor Cells of the Gut

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...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-09, Vol.250 (2), p.511-515
Main Authors: Glassmeier, Günter, Höpfner, Michael, Riecken, Ernst-Otto, Mann, Benno, Buhr, Heinz, Neuhaus, Peter, Meyerhof, W., Scherübl, Hans
Format: Article
Language:English
Subjects:
Calcium Channel Blockers - pharmacology
Calcium Channels - drug effects
Calcium Channels - physiology
calcium signalling
carcinoid cells
Hormones - pharmacology
Humans
Intestinal Neoplasms - metabolism
Intestinal Neoplasms - physiopathology
Neuroendocrine Tumors - metabolism
Neuroendocrine Tumors - physiopathology
Octreotide - pharmacology
Patch-Clamp Techniques
Signal Transduction - drug effects
Signal Transduction - physiology
somatostatin
Tumor Cells, Cultured
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Summary: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 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-sensitive L-type VDCC.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.9344