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. 1992 Dec 15;288(Pt 3):847–851. doi: 10.1042/bj2880847

Somatostatin inhibits vasopressin-stimulated phosphoinositide hydrolysis and influx of extracellular calcium in clonal hamster beta (HIT) cells.

S B Richardson 1, T Laya 1, M Gibson 1, N Eyler 1, M Van Ooy 1
PMCID: PMC1131964  PMID: 1361725

Abstract

Vasopressin (VP) stimulates insulin secretion and inositol phosphate (InsP) production in clonal hamster beta cells (HIT) via a cyclic AMP-independent V1-receptor-mediated signal-transduction pathway. Somatostatin (SRIF) inhibited VP-stimulated insulin secretion, and the effects of SRIF were abolished by pretreatment with pertussis toxin. The Ca(2+)-channel blockers verapamil and nifedipine also inhibited VP-stimulated insulin secretion during 20 min incubations, but verapamil was ineffective at 2 min, and the effects of SRIF and nifedipine together were not addictive. SRIF failed to inhibit further the attenuated insulin response to VP in Ca(2+)-free medium. VP-stimulated InsP production was also inhibited by SRIF in a pertussis-toxin-sensitive manner. Whereas VP-stimulated insulin secretion was almost completely inhibited by SRIF at an equimolar concentration, VP-stimulated InsP production was much less sensitive to inhibition by SRIF, even at a 100-fold excess concentration. VP increased cytosolic Ca2+ in HIT cells loaded with fura 2, the fluorescent Ca2+ indicator. The increase was biphasic, with an initial rapid spike increase followed by a prolonged second phase. Both SRIF, at a concentration which inhibited VP-stimulated insulin secretion but not InsP production, and verapamil failed to inhibit the rapid spike increase in intracellular Ca2+, but did inhibit the second phase. We conclude that VP induces biphasic changes in cytosolic Ca2+, secondary to mobilization of intracellular Ca2+ and influx of extracellular Ca2+. SRIF inhibits insulin secretion by interrupting influx of extracellular Ca2+, likely by inhibiting Gi-subunit activity. Inhibition of VP-stimulated phosphoinositide hydrolysis, which is also pertussis-toxin-sensitive, may represent an additional mechanism of action of SRIF.

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Selected References

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