Effects of metoclopramide and isoprenaline in the rat vas deferens; interactions with alpha-adrenoceptors.

1 Metoclopramide (2.8 to 280 microM) augmented contractions of rat vas deferens preparations induced by field stimulation (6 Hz for 1 s). This effect was antagonized by phentolamine (0.1 microM). Metoclopramide (2.8 to 280 microM) did not affect phenylephrine-induced contractions. 2 Metoclopramide (2.8 to 280 microM) antagonized the inhibitory effects of clonidine on the contractions induced by field stimulation, but not the inhibitory effects of purine nucleosides. 3 From these results it is concluded that metoclopramide (2.8 to 280 microM) is a presynaptic alpha-adrenoceptor antagonist in the rat vas deferens. 4 Following beta-adrenoceptor blockade with (+/-)-propranolol (3.3 microM), (-)-isoprenaline (0.47 to 14 microM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 microM) and by phentolamine (0.1 to 10 microM), indicating that isoprenaline may stimulate presynaptic alpha-adrenoceptors in this preparation.