SK&F 104078 Identifies Subtypes of Prejunctional α2-adrenoceptors in the Rat vas deferens

ABSTRACT The alpha -2 adrenoceptor agonists, UK 14,304, xylazine, B-HT 933, B-HT 920, clonidine and M-7, inhibited stimulation-evoked contractions of the rat vas deferens. Rauwolscine antagonized the inhibitory effects of these compounds indicating activation of prejunctional alpha -2 adrenoceptors. Rauwolscine did not discriminate between any of these agonists. In contrast, SK&F 104078 (10 uM) did not antagonize the inhibition of the twitch response induced by UK 14,304, xylazine, B-HT 933 or B-HT 920, but did significantly antagonize the inhibitory effect of clonidine and M-7. SK&F 104078 (10 uM) did not antagonize the inhibitory effect of any of the agonists at prejunctional alpha -2 adrenoceptors in the field-stimulated guinea-pig atria, but was equieffective in inhibiting contractions mediated by prejunctional alpha -2 adrenoceptors in the canine saphenous vein produced by all the agonists. It is concluded that SK&F 104078 selectively inhibits postjunctional alpha -2 adrenoceptors in canine saphenous vein, and does not block prejunctional alpha -2 adrenoceptors in guinea pig atria. The results also suggest that there are subtypes of prejunctional alpha -2 adrenoceptors in the rat vas deferens which may be selectively stimulated by some alpha -2 adrenoceptor agonists and can be discriminated by SK&F 104078, but not by rauwolscine.