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

1. Growth hormone secretion, exchangeable cellular sodium and calcium concentrations measured by 22Na and 45Ca incorporation, and efflux of 45Ca were studied in dispersed bovine anterior pituitary cells. 2. Addition of veratridine (100 microM), an activator of sodium channels, increased exchangeable sodium and calcium 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 calcium was decreased below 0.1 mM. 3. The increases in growth hormone secretion, exchangeable calcium concentration and 45Ca efflux from prelabelled cells caused by veratridine were abolished by addition of the calcium antagonist verapamil (20 microM). Verapamil also reduced the rise in exchangeable sodium caused by veratridine and increased the resting exchangeable sodium concentrations. 4. The peptide somatostatin (1 micrograms/ml) prevented veratridine-stimulated growth hormone secretion but did not inhibit the increases in exchangeable sodium and calcium caused by veratridine. The peptide itself elicited a transient increase in 45Ca efflux and subsequently partially inhibited veratridine-stimulated 45Ca efflux. 5. The data suggest that anterior pituitary cells possess voltage-sensitive sodium channels. Activation of these channels by veratridine may lead to depolarization and increased entry of calcium via potential-dependent calcium channels, which contributes to a rise in cytoplasmic calcium concentration and the subsequent stimulation of growth hormone secretion. We conclude that the calcium antagonist verapamil may also interact with sodium channels, and that the peptide somatostatin may act on growth-hormone-secreting cells either to prevent the rise in cytoplasmic calcium by hyperpolarizing the cells or to decrease the affinity of a population of calcium binding sites in the cells.