In vivo and in vitro effects of cholecystokinin octapeptide on the release of beta-endorphin-like immunoreactivity

Abstract

The effect of cholecystokinin octapeptide (CCK-8) on the release of beta-endorphin-like immunoreactivity (beta-EpLI) in rats was studied in vivo and in vitro. Intravenous injection of 5 micrograms/100 g body weight of CCK-8 resulted in significant increase in the plasma beta-EpLI level after 10 and 20 min. CCK-8 at concentrations of 10(-10) - 10(-6) M also caused dose-dependent stimulation of beta-EpLI release from dispersed cells of rat anterior pituitary. However, CCK-4 and desulfated CCK-8 had no effect. On gel chromatography, the beta-EpLI released by incubation of the cells with 10(-8) M CCK-8 separated into two components, eluted in the same positions as human beta-lipotropin and human beta-endorphin, respectively. CCK-8 did not stimulate beta-EpLI release in Ca++-free medium. A 23187 at concentrations of 10(-6) - 10(-3) M caused dose-dependent stimulation of beta-EpLI release from the cells. Addition of 2 X 10(-3) M CoCl2, 10(-3) M verapamil or 10(-7) M dexamethasone to the incubation medium inhibited CCK-8-induced beta-EpLI release from the cells. Dibutyryl cyclic GMP (3 X 10(-3) M) inhibited CCK-8-induced beta-EpLI release from the cells. Ouabain (10(-5) M) also stimulated beta-EpLI release but its effect was not additive with that of CCK-8. These results indicate that CCK-8 acts directly and specifically on anterior pituitary cells to stimulate beta-EpLI release and that calcium ion is involved in the mechanism of this effect.