Dopamine modulates peripheral purinergic neurotransmission through multiple presynaptic receptors: tissue-dependent effects.
This study investigated the identity of presynaptic receptors involved in dopaminergic modulation of purinergic transmission in peripheral tissues including isolated rat vas deferens and urinary bladder. Isometric muscle twitches were established in the two tissues by low frequency electric field-stimulation (0.05 Hz, 1-ms duration, and supramaximal voltage). Exposure to prazosin, 50 nmol l-1 (vas deferens), or atropine, 3 micromol l-1 (urinary bladder), had no effect on the developed twitches. In contrast, desensitisation of P2X-purinoceptors by alpha,beta-methylene ATP (alpha,beta-mATP, 30 micromol l-1) abolished the twitches in both tissues, confirming their purinergic origin. Dopamine (1.8x10(-7) to 4.2x10(-5) mol l-1) reduced the twitch response in a concentration-related manner. Yohimbine (alpha2-adrenoceptor antagonist, 0.3 micromol l-1) significantly (P<0.05) attenuated the inhibitory effects of dopamine and caused an upward shift in the concentration-response curves in the vas deferens and the urinary bladder. On the other hand, a blockade of DA2-dopaminoceptors by domperidone (1 micromol l-1) produced significant (P<0.05) reductions in dopamine responses only in rat vas deferens, with no effect in the urinary bladder. These data suggest that dopamine exerts inhibitory influences on purinergically-mediated muscle twitches in rat vas deferens and urinary bladder. More importantly, the nature of presynaptic receptors (alpha2-adrenergic and/or DA2-dopaminergic) involved in mediating dopamine effects is dependent on the tissue under investigation.
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
M M
MM
El-Mas
A I
AI
Elmallah
A G
AG
Omar
F
F
Sharabi
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000502:physiology*; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
D018377:Neurotransmitter Agents; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic; D011983:Receptors, Purinergic; D004298:Dopamine