Inhibition of urinary bladder contractions by a spinal action of morphine and other opioids.
Systemic morphine (1.0 mg/kg i.v. or s.c.) consistently inhibited spontaneous urinary bladder contractions recorded isometrically in the anesthetized rat. This effect was reversed by intrathecal (i.t.) naloxone (1-4 micrograms) at doses which were ineffective systemically. Intrathecal morphine was also inhibited bladder activity when administered into cervical, thoracic or lumbar regions but was faster acting and more effective when injected i.t. directly in the vicinity of the lumbo-sacral cord. The effect of morphine was dose-related and appeared to be a stereospecific opiate effect being observed with i.t. levorphanol but not with dextrorphan. Bladder inhibition by i.t. morphine at low doses could be overcome by increasing the intravesicular pressure. Intrathecal morphine was also reversed by i.t. (1-2 micrograms) or s.c. (0.5 mg/kg) naloxone but not by i.c.v. naloxone (1-2 micrograms). Intrathecal naloxone in naive animals increased bladder contraction frequency and intravesicular pressure only at high doses (10-20 micrograms i.t.). Bladder activity was consistently inhibited by [D-Ala2,MePhe4,Gly-(ol)5] enkephalin (mu agonist) and [D-Ala2-D-Leu5]enkephalin (delta agonist) but was unaffected by U-50, 488H i.t., (kappa agonist). The observations support the hypothesis that spinal opioid mechanisms are involved in the neurogenic control of bladder function and that systemically or i.t. administered opioid drugs mediate inhibition of bladder motility by spinal mechanisms involving mu and delta opioid receptors.
D000818:Animals; D004231:Diuresis / Q000187:drug effects; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects*
D009294:Narcotics; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine