Effects Of Cannabinoid Receptor Agonists On Urinary Bladder Tissues

[Julie Gardener]

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

R S Martin, L A Luong, N J Welsh, R M Eglen, G R Martin, and S J MacLennan
Br J Pharmacol. 2000 April

Abstract

1. This study investigated the cannabinoid receptor, known to inhibit neuronally-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 bladder observed previously was confirmed in this study by the rank order of agonist potencies: CP 55940WIN 55212-2>HU 210>JWH 015>anandamide, the high affinity of the CB1 selective antagonist, SR 141716A (apparent pKB 8.7), and the low affinity of the CB2 antagonist, SR 144528 (apparent pKB<6.5). In these studies, SR 141716A (10—100nM) significantly potentiated electrically-evoked contractions in this tissue by an undetermined mechanism.

3. A similar rank order of agonist potencies was determined in rat isolated bladder sections (CP 55, 940WIN 55212-2>JWH 015). In this tissue, the maximal inhibitory effect of all agonists was lower than 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 (30nM) or SR 144528 (100nM), reversed the inhibitory effect of WIN 55212-2 (apparent pKB=8.4 and 8.0, respectively) or JWH 015 (apparent pKB=8.2 and 7.4, respectively). These findings may demonstrate pharmacological differences between the rat and mouse orthologues of the CB1 receptor. Alternatively, they may be attributed to a mixed population of CB1 and CB2 receptors that jointly influence neurogenic contraction of the rat bladder, but cannot be differentiated without 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 findings suggest that the effect of cannabinoid agonists to inhibit neurogenic contraction of the mouse and rat bladder is not conserved across all mammalian species.

Source with Graphs, Charts and Links: Effects of cannabinoid receptor agonists on neuronally-evoked contractions of urinary bladder tissues isolated from rat, mouse, pig, dog, monkey and human