title: The action of halothane on stimulus-secretion coupling in clonal (GH3) pituitary cells.
abstract: The effect of halothane on the physiological response to excitatory stimuli was assessed in clonal (GH3) pituitary cells. Halothane, at concentrations used to produce general anesthesia in animals (0.25-0.76 mM), inhibited thyrotropin-releasing hormone (TRH)-induced prolactin (PRL) secretion. The sustained (extracellular calcium-dependent) phase of PRL secretion was 70 +/- 7% inhibited by the highest concentration of halothane tested (0.76 mM); 50% inhibition was produced by approximately 0.4 mM halothane. The early (largely inositol trisphosphate-mediated) phase of secretion was less sensitive to halothane; 0.76 mM halothane produced 18 +/- 2% inhibition of the early phase of secretion. Consistent with these observations, halothane inhibited (IC50 approximately 0.45 mM) the sustained phase of the TRH-induced rise in intracellular calcium ([Ca2+]i) to a greater extent than the initial [Ca2+]i peak. The sustained phase of the [Ca2+]i elevation was inhibited by 75 +/- 7% at the highest concentration of halothane tested (0.76 mM), whereas the peak [Ca2+]i was only inhibited by 14 +/- 5%, consistent with the observation that halothane did not inhibit TRH-stimulated inositide hydrolysis in these cells. Halothane (0.5 mM) did not inhibit phorbol ester- or ionomycin-induced PRL secretion, indicating that halothane has inconsequential effects on the secretory apparatus. Halothane (0.5 mM) also inhibited KCl-induced PRL secretion by 50-80% and the corresponding KCl-induced rise in [Ca2+]i by 68 +/- 6%. These data indicate that halothane inhibits secretagogue-stimulated PRL secretion by reducing the elevation of [Ca2+]i produced by calcium (Ca2+) influx.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anesthesiology Research, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: R C
authors.initials: RC
authors.lastname: Stern
authors.forename: J
authors.initials: J
authors.lastname: Herrington
authors.forename: C J
authors.initials: CJ
authors.lastname: Lingle
authors.forename: A S
authors.initials: AS
authors.lastname: Evers
mesh_terms: D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011388:Prolactin / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D015759:Ionomycin; D009553:Nimodipine; D013973:Thyrotropin-Releasing Hormone; D011189:Potassium Chloride; D011388:Prolactin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D006221:Halothane