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 EC(50) 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 mu M).

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.