M3 muscarinic receptors mediate contraction of human urinary bladder

Since muscarinic receptors appear to be the physiologically most important control system for urinary bladder contraction, we have characterized the receptor subtype mediating contraction in response to the muscarinic agonist carbachol in the human bladder. Experiments were based on four antagonists, the non-selective atropine, the M-1-selective pirenzepine, the M-2-selective methoctramine and the M-3-selective darifenacin. All antagonists yielded Schild-plots with a slope close to unity. The order of potency (atropine greater than or equal to darifenacin > pirenzepine > methoctramine) as well as the estimated antagonist affinities suggested that contraction of the human bladder occurs predominantly if not exclusively via the M-3 receptor.