The Journal of Neuroscience, August 15, 2002, 22(16):7147-7153
Contrasting Effects of WIN 55212-2 on Motility of the Rat
Bladder and Uterus
Natalia
Dmitrieva and
Karen J.
Berkley
Program in Neuroscience, Florida State University, Tallahassee,
Florida 32306-1270
Both the uterus and bladder contain cannabinoid (CB)
receptors whose functions are poorly understood. Here, in
urethane-anesthetized female rats in metestrus, we simultaneously
compared the effects of close-arterial injections of the cannabinoid
receptor agonist WIN 55,212-2 (WIN2) on uterine contractions
(amplitude and rate) and micturition thresholds (MT) assessed by
cystometry. Five doses of WIN2 were delivered (0.01, 0.1, 0.5, 1, and
1.5 µmol/kg) in three groups: (1) controls; (2) after bladder
inflammation with intravesicular turpentine; and (3) after bilateral
hypogastric neurectomy (HYPX). In some rats, drugs were delivered via
the tail vein. Regarding bladder, WIN2 dose-dependently reduced MTs in
all groups. Both bladder inflammation and HYPX significantly increased
this effect. Regarding uterus, WIN2 dose-dependently increased uterine
contraction amplitude. Bladder inflammation or HYPX significantly
decreased this effect. Coinjection of the CB1 antagonist SR141716A (SR)
(1.5 µmol/kg) and WIN2 (0.5 µmol/kg) abolished or reduced the
effects of WIN2 in both organs. SR alone had significant effects
only after HYPX, reducing both MT and uterine contraction amplitude.
The vehicle (0.4% DMSO) and inactive enantiomer
S(
)-WIN 55,212-3 were both ineffective.
Close-arterial injections of WIN2 (0.5 µmol/kg) produced
significantly larger effects in both organs than tail vein injections.
These results indicate that, whereas WIN2 reduces bladder motility, it
mainly increases uterine motility, likely via CB1 receptors located in the two organs. The opposing effects of bladder inflammation and HYPX
on the potency of WIN in the two organs suggest a neurally mediated
viscero-visceral interaction in which bladder inflammation influences uterine CB1 sensitivity, possibly by inhibiting adrenergic input to the uterus.
Key words:
cannabinoid; hypogastric nerve; inflammation; pelvic
organs; lower urinary tract; reproductive organs
Copyright © 2002 Society for Neuroscience 0270-6474/02/22167147-07$05.00/0
Previous Article | Next Article
