Release of 3H-adrenaline from an isolated intact preparation of the rabbit adrenal gland: no evidence for release modulatory alpha-adrenoreceptors.

1 The possibility that catecholamine secretion from the rabbit adrenal gland is subject to modulation by a mechanism involving alpha-adrenoreceptors was investigated in an isolated preparation of the gland. 2 Intact left adrenal glands from the rabbit were perfused with Krebs-Henseleit solution through their vasculature. The adrenal catecholamine stores were radiolabelled with 3H-adrenaline and subsequently, efflux of the radiolabel was elicited by stimulation of an attached segment of splanchnic nerve (60 s at 5 Hz). In some experiments, efflux of radiolabel was elicited by perfusion with potassium-enriched Krebs-Henseleit solution (30 mM). 3 Radioactivity released in response to nerve stimulation was accounted for almost entirely by (3H)-adrenaline. Stimulation-induced (S-I) efflux was abolished by 0.1 microM tetrodotoxin and by omission of calcium from the perfusion medium and was reduced by approximately 55% by 100 microM hexamethonium. 4 S-I efflux was enhanced to approximately 150% of control S-I efflux in the presence of 10 microM phenoxybenzamine; however, 3 microM phentolamine and yohimbine in concentrations of 0.1 and 1.0 microM had no effect; in a higher concentration (10 microM) yohimbine reduced S-I efflux by approximately 50%. It is likely that the effect of phenoxybenzamine in enhancing S-I efflux is due to blockade of reuptake of 3H-adrenaline since cocaine (30 microM) enhanced release to a similar extent. 5 S-I efflux was not altered in the presence of the alpha-adrenoreceptor agonists noradrenaline (0.1 microM), clonidine (1 microM) or oxymetazoline (10 microM). 6 Release of radiolabel evoked by perfusion with 30 mM potassium solution was unaltered in the presence of phentolamine (3 microM) of clonidine (1 microM). 7 These findings do not support the existence in the rabbit adrenal gland of a mechanism involving alpha-adrenoreceptors through which catecholamine secretion may be modulated.