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 (GH,) 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 f 7% inhibited by the highest concentration of halothane tested (0.76 mM); 50% inhibition was produced by x0.4 mr.! halothane. The early (largely inositol trisphosphate-mediated) phase of secretion was less sensitive to halothane; 0.76 mM halothane produced 16 + 2% inhibition of the early phase of secretion. Consistent with these observations, halothane inhibited (IC,, = 0.45 mM) the sustained phase of the TRH-induced rise in intracellular calcium ([Ca*+]J to a greater extent than the initial [Ca*+p by 66 f 6%. These data indicate that halothane inhibits secretagogue-stimulated PRL secretion by reducing the elevation of [Ca2+li produced by calcium (Caz+) influx. The effects of halothane on average resting membrane potential and on the average KCI- and TRH-induced membrane depolarization were measured to determine if alterations in membrane potential might be responsible for the effect of halothane on the secretagogue-induced elevations of [Ca2+li. In nimodipine-treated cells, it was found that halothane neither altered resting membrane potential nor affected TRH- or KCI-induced depolarization. These findings support the view that halothane can act to inhibit the phys