Regulation of excitation-secretion coupling by thyrotropin-releasing hormone (TRH): Evidence for TRH receptor-ion channel coupling in cultured pituitary cells

Summary 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 (–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.