alpha-Adrenoceptor stimulated lymphocytes trigger the mechanical response of vas deferens: participation of arachidonic acid metabolites.
Normal human lymphocytes (L) (8 X 10(5) ml-1) incubated with methoxamine (Me) (1 X 10(-7) M) (Me-L) triggered the mechanical response of the isolated vas deferens of the rat. L or Me alone did not modify this contractile activity at the concentrations cited above. Me alone (10(-6) to 10(-3) M) increased the tension of the vas. In the presence of L (8 X 10(5) ml-1) the dose-response curve to Me shifted to the left and the efficacy of Me was enhanced. Inhibitors of alpha 1-adrenoceptors completely blocked the reaction between Me and L while drugs that block alpha 1 and alpha 2-adrenoceptors reduced the reaction between Me-L and the vas deferens. Direct contact of Me-L with the assay organ was not necessary. Cell-free supernatants of L exposed to Me (Me-L supernatants) elicited the reaction in the same way as Me-L. This effect required the continuous presence of Me since dialyzed Me-L supernatants were inactive. Inhibitors of lipoxygenase(s) completely blocked the positive inotropic effect of Me-L or of Me-L supernatants. Inhibitors of cyclo-oxygenase potentiated this effect. These results suggest that Me reacts with alpha 1-adrenoceptors of L. From this reaction, soluble factors are released that potentiate the alpha-adrenoceptor stimulatory effect of Me on the vas deferens as a consequence of the release of oxidative products of the lipoxygenase/s pathway of arachidonic acid.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D008729:Methoxamine