Presynaptic alpha 2-adrenoceptors exclusively sensitive to agonists of phenylethylamine structure on the sympathetic nerves of the human gall bladder artery.
The influence of alpha 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 [3H]noradrenaline. The preparations were stimulated at 2 Hz for 3 min (360 shocks each of 1 ms duration two times (S1 and S2)). Both the L-noradrenaline and alpha-methylnoradrenaline (10(-6) M) significantly reduced (S2/S1 = 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 [3H]noradrenaline. Yohimbine (10(-6) M), CH-38083, which is a new, selective alpha 2-adrenoceptor antagonist (10(-7) M) and prazosin (10(-6) M) enhanced the evoked release of radioactivity, where S2/S1 were 2.50 +/- 0.19; 2.99 +/- 0.32; 1.48 +/- 0.05, respectively. Administering the alpha 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 alpha-methylnoradrenaline on the release of radioactivity. Our results suggest that one type of presynaptic alpha 2-adrenoceptor modulates the release of noradrenaline evoked by electrical stimulation of the human cystic artery. This receptor is sensitive to alpha 2-adrenoceptor agonists which have a phenylethylamine structure, but is insensitive to imidazolines and guanfacine.
Kapocsi
J
J
Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.
Zimanyi
I
I
Farsang
C
C
Vizi
E S
ES
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001158:Arteries / Q000294:innervation* / Q000502:physiology; D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005704:Gallbladder / Q000098:blood supply*; D006801:Humans; D066298:In Vitro Techniques; D008771:Nordefrin / Q000494:pharmacology; D009638:Norepinephrine / Q000031:analogs & derivatives / Q000378:metabolism*; D010627:Phenethylamines; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D001599:Berberine; C048886:7,8-(methylenedioxy)-14-hydroxyberbane; D015016:Yohimbine; C029261:phenethylamine; D008771:Nordefrin; D009638:Norepinephrine; D011224:Prazosin