Regulation of excitation-secretion coupling by thyrotropin-releasing hormone (TRH): evidence for TRH receptor-ion channel coupling in cultured pituitary cells.
The electrophysiological and secretory properties of a well-studied clonal line of rat anterior pituitary cells (GH3) have been compared with a new line of morphologically distinct cells derived from it (XG-10). The properties of the latter cells differ from the parent cells in that they do not have receptors for thyrotropin-releasing hormone and their basal rate of secretion is substantially higher (ca. three- to fivefold). While both cell types generate Ca++ spikes, the duration of the spike in XG-10 cells (ca. 500 msec) is about 2 orders of magnitude longer than that in GH3 cells (5-10 msec). The current-voltage characteristics of the two cell types are markedly different; the conductance of GH3 cells is at least 20-fold higher than XG-10 cells when cells are depolarized to more positive potentials than the threshold for Ca++ spikes (approximately -35 mV). While treatment of GH3 cells with the secretagogues tetraethylammonium chloride or thyrotropin-releasing hormone decreases the conductance in this voltage region to approximately the same as that for XG-10 cells, the electrophysiological and secretory properties of XG-10 cells are unaffected by treatment with either of these agents. Results of this comparative study suggest that XG-10 cells lack tetraethylammonium-sensitive K+ channels. The parallel loss of thyrotropin-releasing hormone receptor binding activity and of a K+ channel in XG-10 cells implies that the thyrotropin-releasing hormone receptor may be coupled with, or be an integral part of, this channel. Apparently thyrotropin-releasing hormone, like tetraethylammonium chloride, acts by inhibiting K+ channels resulting in a prolongation of the action potential, promoting Ca++ influx and subsequently enhancing hormone secretion.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000503:physiopathology; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology
D007473:Ion Channels; D011956:Receptors, Cell Surface; D018025:Receptors, Thyrotropin-Releasing Hormone; D013757:Tetraethylammonium Compounds; D013973:Thyrotropin-Releasing Hormone; D019789:Tetraethylammonium