Drug Effects on Epineprine Release from Rat Adrenal Medulla Homogenates and Granule Preparations. ∗

Abstract

Summary

1. Adrenal homogenates and fractionated medullary granule suspensions from rats were incubated in various media at several temperatures with and without addition of various concentrations of drugs, after which adrenaline concentration was measured in the centrifuged particulates and the supernatant. 2. Both homogenates and granule suspensions showed minimal spontaneous release of adrenaline at O°C, markedly increased with temperature. All drug incubations were carried out routinely at O°C. In many instances determinations were repeated at increased temperature and drug concentration under experimental conditions which approximated those of other investigators who studied the release of catecholamines from the chromaffin granules of other species. 3. Thirteen of the 35 drugs examined modified the release of adrenaline from the rat chromaffin granules. a) Ten of these were previously reported to increase the release in vitro in other species. They were chlorpromazine, compazine, CH₃-promazine, chlorpromazine sulfoxide, imipramine, PCMB, Serpasil, Serpasil Suspending Vehicle, ephedrine and methamphetamine. b) LSD and mescaline increased the release from the rat granules; they had been previously reported ineffective in other species. c) Serotonin slowed the release; this had not been previously reported.

4. Twenty-two of the 35 drugs examined were ineffective as releasers when incubated with the rat chromaffin granules. a) At least 6 of these, which we found ineffective, were previously reported effective in other species. They were reserpine, TM-10, tyramine, cocaine, dibenzyline and 48-80. b) Reserpine deserves special comment because, in other species, it has been reported to be effective as a releaser at high concentrations and as an inhibitor of spontaneous release at lower concentrations. Neither of these effects was observed in comparable experiments with rat medullary granules. c) The 16 remaining drugs which we found ineffective were: histamine, acetylcholine, guanethidine, bretylium, insulin, RO-1-9569, physostigmine, tremorine, librium, nialamide, iproniazid, JB-329, bufotenin, DOPA, sodium fluoride, and sodium cyanide.