Inhibition by somatostatin of bovine growth hormone secretion following sodium channel activation.

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Abstract
Growth hormone secretion, exchangeable cellular Na and Ca concentrations measured by 22Na and 45Ca incorporation, and efflux of 45Ca were studied in dispersed bovine anterior pituitary cells. Addition of veratridine (100 .mu.M), an activator of Na channels, increased exchangeable Na and Ca concentrations in the cells, the efflux of 45Ca from prelabelled cells, and caused a biphasic stimulation of the rate of growth hormone secretion. Secretion of growth hormone was not stimulated when the extracellular Ca was decreased < 0.1 mM. The increases in growth hormone secretion, exchangeable Ca concentration and 45Ca efflux from prelabelled cells caused by veratridine were abolished by addition of the Ca antagonist verapamil (20 .mu.M). Verapamil also reduced the rise in exchangeable Na caused by veratridine and increased the resting exchangeable Na concentrations. The peptide somatostatin (1 .mu.g/ml) prevented veratridine-stimulated growth hormone secretion but did not inhibit the increases in exchangeable Na and Ca caused by veratridine. The peptide itself elicited a transient increase in 45Ca efflux and subsequently partially inhibited veratridine-stimulated 45Ca efflux. Anterior pituitary cells probably possess voltage-sensitive Na channels. Activation of these channels by veratridine may lead to depolarization and increased entry of Ca via potential-dependent Ca channels, which contributes to a rise in cytoplasmic Ca concentration and the subsequent stimulation of growth hormone secretion. The Ca antagonist verapamil may also interact with Na channels, and the peptide somatostatin may act on growth-hormone-secreting cells either to prevent the rise in cytoplasmic Ca by hyperpolarizing the cells or to decrease the affinity of a population of Ca binding sites in the cells.