Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6-23 cells: possible involvement of a pertussis toxin-sensitive G-protein.
The mechanisms by which somatostatin inhibits hormone release are complex and involve, among other things, reduction of both intracellular cAMP and intracellular calcium. We studied the influence of the long-acting somatostatin analogue octreotide on norepinephrine (NE)-induced changes in intracellular calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell line, rMTC 6-23. Increases in the extracellular calcium concentration ([Ca2+]e) induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also could be blocked by the addition of EGTA or verapamil. Octreotide prevented or reversed the NE-induced increase in [Ca2+]i. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+]e, most probably through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated rise in [Ca2+]i by a pertussis toxin-sensitive G-protein, most probably through a direct effect on NE-activated calcium channels.
Zink
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Abteilung Innere Medizin I, Endokrinologie und Stoffwechsel Universitätsklinik Heidelberg, Germany.
Raue
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D000818:Animals; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D015282:Octreotide / Q000494:pharmacology; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D002116:Calcitonin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D015282:Octreotide; D002118:Calcium; D009638:Norepinephrine