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

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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.

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Author notes

  1. John P. Reuben

    Present address: Merck Sharp & Dohme Research Laboratories, Merck Institute for Therapeutic Research, 07065, Rahway, New Jersey

Authors and Affiliations

  1. Merck Sharp & Dohme Research Laboratories, Merck Institute for Therapeutic Research, 07065, Rahway, New Jersey

    Gregory J. Kaczorowski & Richard L. Vandlen

  2. Department of Neurology, Columbia University, 10032, New York, New York

    George M. Katz & John P. Reuben

  3. Marine Biological Laboratory, 02543, Woods Hole, Massachusetts

    George M. Katz & John P. Reuben

Authors
  1. Gregory J. Kaczorowski
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  2. Richard L. Vandlen
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  3. George M. Katz
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  4. John P. Reuben
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Kaczorowski, G.J., Vandlen, R.L., Katz, G.M. et al. Regulation of excitation-secretion coupling by thyrotropin-releasing hormone (TRH): Evidence for TRH receptor-ion channel coupling in cultured pituitary cells. J. Membrain Biol. 71, 109–118 (1983). https://doi.org/10.1007/BF01870679

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  • DOI: https://doi.org/10.1007/BF01870679

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