Dopamine modulates peripheral purinergic neurotransmission through multiple presynaptic receptors: Tissue-dependent effects

This study investigated the identity of presynaptic receptors involved in d opaminergic modulation of purinergic transmission in peripheral tissues inc luding isolated rat vas deferens and urinary bladder. Isometric muscle twit ches were established in the two tissues by low frequency electric field-st imulation (0.05 Hz, 1-ms duration, and supramaximal voltage). Exposure to p razosin, 50 nmol l(-1) (vas deferens), or atropine, 3 mu mol l(-1) (urinary bladder), had no effect on the developed twitches. In contrast, desensitis ation of P-2x- purinoceptors by alpha,beta-methylene ATP (alpha,beta-mATP, 30 mu mol l(-1)) abolished the twitches in both tissues, confirming their p urinergic origin. Dopamine (1.8 x 10(-7) to 4.2 x 10(-5) mol l(-1)) reduced the twitch response in a concentration-related manner. Yohimbine (alpha(2) -adrenoceptor antagonist, 0.3 mu mol l(-1)) significantly (P < 0.05) attenu ated the inhibitory effects of dopamine and caused an upward shift in the c oncentration-response curves in the vas deferens and the urinary bladder. O n the other hand, a blockade of DA(2)-dopaminoceptors by domperidone (1 mu mol l(-1)) produced significant (P < 0.05) reductions in dopamine responses only in rat vas deferens, with no effect in the urinary bladder. These dat a suggest that dopamine exerts inhibitory influences on purinergically-medi ated muscle twitches in rat vas deferens and urinary bladder. More importan tly, the nature of presynaptic receptors (alpha(2)-adrenergic and/or DA(2)- dopaminergic) involved in mediating dopamine effects is dependent on the ti ssue under investigation, (C) 1999 The Italian Pharmacological Society.