α-Adrenoceptor stimulated lymphocytes trigger the mechanical response of vas deferens: participation of arachidonic acid metabolites

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Abstract
1 Normal human lymphocytes (L) (8 × 105 ml−1) incubated with methoxamine (Me) (1 × 10−7 M) (Me-L) triggered the mchanical response of the isolated vas deferens of the rat. L or Me alone did not modify this contractile activity at the concentrations cited above. 2 Me alone (10−6 to 10−3 M) increased the tension of the vas. In the presence of L (8 × 105 ml−1) the dose-response curve to Me shifted to the left and the efficacy of Me was enhanced. 3 Inhibitors of α1-adrenoceptors completely blocked the reaction between Me and L while drugs that block α1 and α2-adrenoceptors reduced the reaction between Me-L and the vas deferens. 4 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. 5 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. 6 These results suggest that Me reacts with α1-adrenoceptors of L. From this reaction, soluble factors are released that potentiate the α-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.