Characterization of the Muscarinic Cholinoceptors in the Human Detrusor

Abstract

Contractions of the human detrusor are thought to be mediated mainly via cholinergic muscarinic receptors. A receptor-binding technique with 1-quinuclidinyl[phenyl 4-3H]benzilate ((-)3H-QNB was used as radioligand to directly demonstrate the presence of muscarinic receptors in homogenates of the human detrusor. The binding of (-)3H-QNB was of high affinity (KD = (1.2 .+-. 0.1) .times. 10-10 M), saturable (Ro = 160 .+-. 15 fmol/mg protein) and possessed the pharmacological specificity expected of an interaction with muscarinic receptors. Muscarinic receptor antagonists were bound to a virtually uniform population of sites, whereas muscarinic receptor agonists recognized more than 1 population of muscarinic binding sites. The affinities of a series of antimuscarinic drugs, determined in competition experiments with (-)3H-QNB, were found to correlate with the capacity to inhibit carbachol-induced contractions in isolated human bladder muscle. Binding data together with the functional data indicated that the human detrusor does not contain any significant number of muscarinic spare receptors. A selective effect on the muscarinic receptors of human bladder is not possible to obtain with presently available antimuscarinic agents.