Presynaptic α2-adrenoceptors exclusively sensitive to agonists of phenylethylamine structure onthe sympathetic nerves of the human gall bladder artery

Abstract

The influence of α 2 -adrenoceptor agonists and antagonists on the release of noradrenaline was studied in human gall bladder (cystic) artery preparations, in which transmitter stores were labelled with [ 3 H]noradrenaline. The preparations were stimulated at 2 Hz for 3 min (360 shocks each of 1 ms duration two times (S 1 and S 2 )). Both the l -noradrenaline and α-methylnoradrenaline (10 −6 M) significantly reduced (S 2 /S 1 =0.27±0.05; 0.43±0.04, respectively), whilst clonidine, xylazine and guanfacine at 10 −6 M failed to affect the stimulation evoked release of [ 3 H]noradrenaline. Yohimbine (10 −6 M), CH-38083, which is a new, selective α 2 -adrenoceptor antagonist (10 −7 M) and prazosin (10 −6 M) enhanced the evoked release of radioactivity, where S 2 /S 1 were 2.50±0.19; 2.99±0.32; 1.48±0.05, respectively. Administering the α 2 -antagonists and prazosin together, we were unable to demonstrate an additive effect. Yohimbine and CH-38083 prevented, while prazosin reduced, the inhibitory effects of l -noradrenaline or α-methyl-noradrenaline on the release of radioactivity. Our results suggest that one type of presynaptic α 2 -adrenoceptor modulates the release of noradrenaline evoked by electrical stimulation of the human cystic artery. This receptor is sensitive to α 2 -adrenoceptor agonists which have a phenylethylamine structure, but is insensitive to imidazolines and guanfacine.