Reversal by pronethalol of dibenamine blockade: a study on the seminal vesicle of the guinea-pig.

1. The guinea-pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving alpha-adrenoceptive receptors, because no beta-receptors were found in this preparation.2. Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7.1 x 10(-6)M, 1.5 x 10(-5)M and 2.7 x 10(-5)M, respectively.3. Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine.4. Pronethalol (6.8 x 10(-5)M) reversed the alpha-receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine.5. Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose-effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol.6. It is assumed that the reversal is dependent on a direct action on alpha-receptors, "spare receptors" being probably involved.