Mu and delta opioid ligands inhibit reflex contractions of the urinary bladder in the rat by different central mechanisms.
The supraspinal and spinal mechanisms of opioid-induced inhibition of reflex contractions of the urinary bladder were studied in female rats, anesthetized with urethane. A variety of central manipulations was made to distinguish the effects produced by [D-Ala2-Me-Phe4-Gly(ol)5]-enkephalin (DAGO), a selective mu-opioid receptor ligand, from those of the delta ligand [2-D-penicillamine, 5-L-penicillamine]-enkephalin (DPLPE), administered by either intracerebroventricular (i.c.v.) or by spinal intrathecal (i.t.) injection. The effect of intraventricular but not of intrathecal administration of DPLPE was abolished 4-5 hr after the systemic administration of reserpine (5 mg/kg, i.p.). Reserpine did not modify the actions of DAGO, given by either route. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, 200 micrograms, i.c.v.) attenuated the effect of DPLPE given intraventricularly but not when given intrathecally, measured 7 days later. The effect produced by DPLPE given by either route was unchanged by pretreatment with 6-hydroxydopamine (6-OHDA, 150 micrograms i.c.v.). Neither 5,7-DHT nor 6-OHDA altered the effect of administrations of DAGO. The effect of DPLPE given intraventricularly was attenuated or abolished, in a dose-related and reversible manner, following the administration of naloxone or methysergide intrathecally but not by phentolamine, propranolol or atropine. The effect of DAGO given intraventricularly was antagonised by naloxone but not by any of the other antagonists. These observations suggested that the supraspinally- and spinally-mediated inhibition of reflex contractions of the urinary bladder produced by mu or delta receptor ligands can be dissociated. The supraspinal effect of DPLPE involved a descending serotoninergic, but not adrenergic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001696:Biomechanical Phenomena; D002490:Central Nervous System / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects*
D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-