Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides.
Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmitter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the superfusion fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10(-5) M) reduced the efflux of 3H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 X 10(-6) M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 X 10(-4) M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D012501:Saphenous Vein / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects*
D000227:Adenine Nucleotides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine