Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.
Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply; D006632:Histamine / Q000494:pharmacology*; D008469:Meclofenamic Acid / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation*; D009433:Neural Inhibition / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D012501:Saphenous Vein / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects
D008469:Meclofenamic Acid; D001285:Atropine; D006632:Histamine; D011433:Propranolol; D009638:Norepinephrine