Characterization of the muscarinic cholinoceptors in the human detrusor.
Contractions of the human detrusor are thought to be mediated mainly via cholinergic muscarinic receptors. In the present study, we used a receptor-binding technique with 1-quinuclidinyl[phenyl 4-3H]benzilate ((-)3H-QNB) 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) X 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 one 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. The results suggest that a selective effect on the muscarinic receptors of human bladder is not possible to obtain with presently available antimuscarinic agents.
D000328:Adult; D000368:Aged; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000032:analysis*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000187:drug effects; D013997:Time Factors; D014316:Tritium; D001743:Urinary Bladder / Q000294:innervation*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D002217:Carbachol