• Bladder;
  • cannabinoid receptor agonists;
  • cannabinoid receptor antagonist;
  • Δ9-tetrahydrocannabinol;
  • AM 630;
  • SR141716A
  • 1
    CP 55,244, (−)−11-hydroxy-dimethylheptyl-Δ8-tetrahydrocannabinol, WIN 55,212-2, Δ9-tetrahydro-cannabinol, nabilone and anandamide each inhibited electrically-evoked contractions of the mouse isolated urinary bladder in a concentration-related manner, their EC50 values being respectively 15.9, 18.27, 27.23, 1327.6, 1341.5 and 4950.3 nM. (+)-11-hydroxy-dimethylheptyl-Δ8-tetrahydrocannabinol was inactive at the highest concentration used (10 μm).
  • 2
    SR141716A (31.62 or 100 nM) produced parallel rightward shifts in the log concentration-response curves of CP 55,244, (−)−11-hydroxy-dimethylheptyl-Δ8-tetrahydrocannabinol, WIN 55,212-2, Δ9-tetrahydrocannabinol and anandamide for inhibition of electrically-evoked bladder contractions. The effect of the antagonist on the log concentration-response curve of CP 55,244 was shown to depend on the concentration of SR141716A used (31.62 to 1000 nM).
  • 3
    The amplitudes of contractions evoked by acetylcholine or β, γ-methylene-L-ATP were not decreased by 316.2 nM CP 55,244 or 3162 nM Δ9-tetrahydrocannabinol. Electrically-evoked contractions were almost completely abolished by 200 nM tetrodotoxin.
  • 4
    The above results support the hypothesis that mouse urinary bladder contains prejunctional CB1 cannabinoid receptors which can mediate inhibition of electrically-evoked contractions, probably by reducing contractile transmitter release.
  • 5
    AM 630 which behaves as a cannabinoid receptor antagonist in the mouse isolated vas deferens did not antagonize the ability of CP 55,244 or Δ9-tetrahydrocannabinol to inhibit electrically-evoked contractions of the mouse bladder.
  • 6
    SR141716A produced small but significant increases in the amplitude of electrically-evoked contractions of the bladder suggesting that this tissue may release an endogenous cannabinoid receptor agonist or that some cannabinoid receptors in this tissue are precoupled to the effector system.