Effects of cannabinoid receptor agonists on neuronally-evoked contractionsof urinary bladder tissues isolated from rat, mouse, pig, dog, monkey and human

1 This study investigated the cannabinoid receptor, known to inhibit neuron ally-evoked contractions of the mouse isolated urinary bladder, in bladder sections isolated from mouse, rat, dog, pig non-human primate or human. 2 The CB1-like pharmacology of the cannabinoid receptor in mouse isolated b ladder observed previously was confirmed in this study by the rank order of agonist potencies: CP 55940 greater than or equal to WIN 55212-2>HU 210>JW H 015>anandamide, the high affinity of the CB1 selective antagonist, SR 141 716A (apparent pK(B) 8.7), and the low affinity of the CB2 antagonist, SR 1 44528 (apparent pK(B)<6.5). In these studies, SR 141716A (10-100 nM) signif icantly potentiated electrically-evoked contractions in this tissue by an u ndetermined mechanism. 3 A similar rank order of agonist potencies was determined in rat isolated bladder sections (CP 55, 940 greater than or equal to WIN 55212-2>JWH 015). In this tissue, the maximal inhibitory effect of all agonists was lower th an in the mouse bladder. Indeed, the effects of both HU 210 and anandamide were too modest to quantify potency accurately. 4 In the rat isolated bladder, SR 141716A (30 nM) or SR 144528 (100 nM), re versed the inhibitory effect of WIN 55212-2 (apparent pK(B) = 8.4 and 8.0, respectively) or JWH 015 (apparent pK(B) = 8.2 and 7.41 respectively). Thes e findings may demonstrate pharmacological differences between the rat and mouse orthologues of the CB1 receptor. Alternatively, they may be attribute d to a mixed population of CB1 and CB2 receptors that jointly influence neu rogenic contraction of the rat bladder, but cannot be differentiated withou t more selective ligands. 5 WIN 55212-2 had no effect on electrically-evoked contractions of bladder sections isolated from dog, pig, cynomolgus monkey and human. These finding s suggest that the effect of cannabinoid agonists to inhibit neurogenic con traction of the mouse and rat bladder is not conserved across all mammalian species.