Effect of picrotoxin on adrenal catecholamine secretion

The effect of picrotoxin (PT) on catecholamine (CA) secretion was investigated in perfused bovine adrenal glands. A low dose of PT (3 microM) enhanced the CA secretion evoked by a 15-min exposure to 1,1-dimethyl-4-phenylpiperazinium (DMPP, a nicotinic agonist; 0.1 mM), but a higher dose (0.3 mM) of PT inhibited the DMPP-evoked CA secretion. The rate of decline of secretory response to the prolonged DMPP stimulation was also accelerated by a higher dose (0.1 mM) of PT. In the dose-response curves for DMPP-evoked CA secretion, the inhibitory action of PT (0.3-1 mM) was more prominent at high doses than at low doses of DMPP. The inhibition pattern was similar to the pattern of a barbiturates blockade. In separate experiments, PT (0.1 mM) augmented calcium (10 mM)- and high potassium (56 mM)-evoked secretory responses. Spontaneous CA secretion was unaffected by PT at the concentrations indicated above. These results indicate that a low dose of PT potentiates, but higher doses inhibit, the adrenal CA secretion by a nicotinic agonist and that the inhibitory effect of PT resembles that of barbiturates.