Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder.

1. CP 55,244, (-)-11-hydroxy-dimethylheptyl-delta 8-tetrahydrocannabinol, WIN 55,212-2, delta 9-tetrahydrocannabinol, 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-delta 8-tetrahydrocannabinol was inactive at the highest concentration used (10 microM). 2. SR141716A (31.62 or 100 nM) produced parallel rightward shifts in the log concentration-response curves of CP 55,244, (-)-11-hydroxy-dimethylheptyl-delta 8-tetrahydrocannabinol, WIN 55,212-2, delta 9-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 beta, gamma-methylene-L-ATP were not decreased by 316.2 nM CP 55,244 or 3162 nM delta 9-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 delta 9-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.