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

1 Normal human lymphocytes (L) (8 × 10 5 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 × 10 5 ml −1 ) the dose‐response curve to Me shifted to the left and the efficacy of Me was enhanced. 3 Inhibitors of α 1 ‐adrenoceptors completely blocked the reaction between Me and L while drugs that block α 1 and α 2 ‐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 α 1 ‐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.