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  • Title: Mechanisms of action of somatostatin on human TSH-secreting adenoma cells.
    Author: Takano K, Ajima M, Teramoto A, Hata K, Yamashita N.
    Journal: Am J Physiol; 1995 Apr; 268(4 Pt 1):E558-64. PubMed ID: 7733252.
    Abstract:
    The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH) secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M) inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)-induced TSH secretion. The mechanisms of this inhibition were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH-induced decrease in [Ca2+]i was independent of the reduction in intracellular cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials, which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp experiments revealed that this membrane hyperpolarization resulted from the activation of an inward-rectifying K+ current through a pertussis toxin-sensitive G protein. Intracellular injection of cAMP (100 microM) through the patch pipette did not abolish the SRIH-induced K+ current, indicating that the activation of SRIH-induced K+ channels was independent of intracellular cAMP. From these data, we concluded that SRIH-induced membrane hyperpolarization was responsible for the [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i, composed of an initial transient increase followed by a sustained increase. SRIH inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
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