EVIDENCE FOR THE PRESENCE OF CANNABINOID CB1 RECEPTORS IN MOUSE URINARY-BLADDER

1 CP 55,244, roxy-dimethylheptyl-Delta(8)-tetrahydrocannabinol, WIN 55 ,212-2, Delta(9)-tetrahydrocannabinol, nabilone and anandamide each in hibited 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. droxy-d imethylheptyl-Delta(8)-tetrahydrocannabinol was inactive at the highes t 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, roxy-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 dep end on the concentration of SR141716A used (31.62 to 1000 nM). 3 The a mplitudes of contractions evoked by acetylcholine or beta, gamma-methy lene-L-ATP were not decreased by 316.2 nM CP 55,244 or 3162 nM Delta(9 )-tetrahydrocannabinol. Electrically-evoked contractions were almost c ompletely abolished by 200 nM tetrodotoxin. 4 The above results suppor t the hypothesis that mouse urinary bladder contains prejunctional CB1 cannabinoid receptors which can mediate inhibition of electrically-ev oked contractions, probably by reducing contractile transmitter releas e. 5 AM 630 which behaves as a cannabinoid receptor antagonist in the mouse isolated vas deferens did not antagonize the ability of CP 55,24 4 or Delta(9)-tetrahydrocannabinol to inhibit electrically-evoked cont ractions of the mouse bladder. 6 SR141716A produced small but signific ant increases in the amplitude of electrically-evoked contractions of the bladder suggesting that this tissue may release an endogenous cann abinoid receptor agonist or that some cannabinoid receptors in this ti ssue are precoupled to the effector system.