Abstract
The involvement of voltage-sensitive Ca2+ channels has been suggested in growth hormone (GH) releasing factor (GRF)-induced GH secretion from somatotrophs. To characterize further the role of L-type Ca2+ channels in GRF-stimulated GH secretion, we examined the effect of nimodipine on GH secretion induced by several secretagogues in perifused dispersed rat anterior pituitary cells. Excess K+ (50 mM)-induced GH secretion was most effectively suppressed by nimodipine among those examined. The ID50 was between 10(-8) and 10(-7) M. One microM nimodipine suppressed 1 nM human GRF (hGRF)-induced GH secretion to 62.1% of the control and 10 microM nimodipine further suppressed it to 33.4% of the control. Dibutyryl cyclic AMP (DBcAMP)-induced GH secretion was less sensitive to inhibition by nimodipine. One mM DBcAMP-induced GH secretion was suppressed to 67.5% of the control by 10 microM nimodipine. Cs+ (20 mM), known to block K+ channels, slightly augmented basal GH secretion, but the same concentration of CS+ caused greater facilitation both in hGRF- and DBcAMP-induced GH secretion. The inhibitory effect of nimodipine was far greater in these CS(+)-augmented responses than that in normal medium. We have previously proposed that hGRF depolarized the somatotrophs in Na(+)-dependent mechanism. This depolarization may elicit the trains of action potentials which involve the activation of L-type Ca2+ channels. Blockade by nimodipine of these L-type Ca2+ channels is time- and voltage-dependent and is maximized by long depolarization. CS+ may prolong the duration of action potentials by blocking the delayed rectifier K+ channels which may provide enough time for nimodipine to block activated L-type Ca2+ channels. These results suggest that L-type Ca2+ channels play a major role in hGRF-induced GH secretion.
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