In vivo and in vitro effects of substance P on the release of beta-endorphin-like immunoreactivity.

The effect of substance P (SP) 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 BW of SP resulted in significant increase in the plasma beta-EpLI level after 15 and 30 min. SP at concentrations of 10(-9) to 10(-6) M also caused dose-dependent stimulation of beta-EpLI release from dispersed cells of rat anterior pituitary. On gel-chromatography, the beta-EpLI released by incubation of the cells with 10(-7) M SP separated into two components, eluted in the same positions as human beta-lipotropin and human beta-Ep, respectively. Release of beta-EpLI from the cells was increased by the addition of K+ at high concentration (53 mM) in a Ca++-dependent manner. Addition of 10(-3) M verapamil to the incubation medium inhibited SP-induced beta-EpLI release from the cells. Ouabain (10(-5) M) had a stimulatory effect on beta-EpLI release which was not additive with that of SP. These results indicate that SP acts directly on the anterior pituitary cells to stimulate beta-EpLI release and that calcium ion is involved in the mechanism of this effect.