title: Mechanisms of action of somatostatin on human TSH-secreting adenoma cells.
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)
authors.affiliation: Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takano
authors.forename: M
authors.initials: M
authors.lastname: Ajima
authors.forename: A
authors.initials: A
authors.lastname: Teramoto
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
mesh_terms: D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009994:Osmolar Concentration; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium