Effects of adrenoceptor antagonists and neuronal uptake inhibitors on dimethylphenylpiperazinium-induced release of catecholamines from the rabbit isolated adrenal gland and guinea-pig atria

AR Collett and DF Story

Isolated rabbit adrenal glands were perfused with Krebs-Henseleit solution at 37 degrees C and the catecholamine storage sites were labeled with [3H]epinephrine. Release of radioactivity was evoked by 2- min periods of perfusion with dimethylphenylpiperazinium (DMPP, 100 microM). DMPP-induced efflux of radioactivity was decreased by desipramine (1 microM), cocaine (30 microM), phenoxybenzamine (1 and 10 microM), phentolamine (1, 3 and 10 microM) and propranolol (1 microM). The reduction in DMPP-induced efflux cannot be accounted for by interactions with alpha adrenoceptors, as prazosin (1 microM) and yohimbine (1 microM) were without effect. There also was no correlation between inhibition of DMPP-induced efflux and ability of the drugs to inhibit catecholamine uptake as phentolamine (1 microM) and propranolol (1 microM) did not affect the incorporation of [3H]epinephrine by the gland. In guinea-pig atria, in which the catecholamine storage sites had been labeled with [3H]norepinephrine, efflux of radioactivity was elicited by 1-min periods of contact with DMPP. DMPP-induced efflux of radioactivity from atria was decreased by desipramine (1 microM), cocaine (30 microM), phenoxybenzamine (1 and 10 microM), phentolamine (1 and 10 microM) and propranolol (1 microM) but not by prazosin (1 microM) or yohimbine (1 microM). The inhibition of DMPP-induced efflux in guinea-pig atria could not be correlated with alpha adrenoceptor antagonism or blockade of neuronal uptake. There were differences between the two preparations in the degree of inhibition of DMPP- induced release produced by the above drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 231, Issue 2, pp. 379-386, 11/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics