Effects of opioid subtypes on detrusor overactivity in rats with cerebral infarction.
OBJECTIVE
In order to determine the influence of different opioid receptor subtypes on detrusor overactivity after left middle cerebral artery (MCA) occlusion, cystometric recordings were obtained in conscious rats.


METHODS
Female Sprague-Dawley rats were used in this study. Control cystometrography was followed by left MCA occlusion. The sham-operated (SO) rats underwent the same procedures except for MCA occlusion. [D-Ala(2), Phe(4), Gly(5)]-enkephalin (DAGO; mu-opioid agonist), [D-Pen(2,5)]-enkephalin (DPDPE; delta1-opioid agonist), deltorpin II (delta2-opioid agonist), and U-50488 (kappa-opioid agonist) were administered intracerebroventricularly at graded doses. The bladder capacity, residual volume, micturition threshold pressure, and bladder contraction pressure were determined. Finally, the volume of the infarction was measured.


RESULTS
The intracerebroventricular administration of DAGO and DPDPE significantly increased the bladder capacity in the cerebrally infarcted (CI) and SO rats, but differences in the changes in bladder capacity between the CI and SO rats were not significant. Deltorpin II did not produce any changes in the bladder capacity in the CI or SO rats at any dose examined. However, the intracerebroventricular administration of U-50488 significantly increased the bladder capacity in the CI rats but not in the SO rats. None of the drugs affected the residual volume, micturition threshold pressure or bladder contraction pressure at any dosage examined. The mean infarcted volumes were not significantly different from those in the vehicle-treated rats.


CONCLUSIONS
These results suggest that the opioid receptor subtypes, mu and delta1 in the brain, are related to the micturition reflex. Furthermore, the kappa opioid agonist might be useful for the suppression of detrusor overactivity caused by cerebral infarction.
Nagasaka
Yasuhiro
Y
Department of Urology, School of Medicine, Kanazawa University, Kanazawa, Japan.
Yokoyama
Osamu
O
Komatsu
Kazuto
K
Ishiura
Yoshiyuki
Y
Nakamura
Yasuo
Y
Namiki
Mikio
M
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D002544:Cerebral Infarction / Q000150:complications / Q000503:physiopathology*; D002552:Cerebral Ventricles; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000008:administration & dosage / Q000627:therapeutic use; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D014563:Urodynamics / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009842:Oligopeptides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-