Identification and characterization of muscarinic cholinergic receptors in the human urinary bladder and parotid gland

Abstract

The binding characteristics of [3H]quinuclidinyl benzilate (QNB) to muscarinic sites in isolated plasma membrane fractions of the human urinary bladder and parotid gland were studied. QNB binding to both preparations was of high affinity and low capacity. Mean values for the apparent dissociation constants (Kd) for binding to membrane preparations from the urinary bladder and parotid glands were 22 and 34 pM and the Bmax values 234 and 456 fmol/mg protein, respectively. Significance of difference between Kd and Bmax values from the two tissues was at the level of P less than 0.005 and P less than 0.05, respectively. QNB binding was inhibited by muscarinic receptor antagonists with varying degree of effectiveness. The mean values for the inhibition constant (Ki) were significantly lower for oxybutynin, amitriptyline, and pirenzepine but higher for secoverine in preparations of the urinary bladder than of the parotid gland. The mean Ki values for quinidine and verapamil were lower in the urinary bladder than that in the parotid gland. Carbachol exhibited a marked selectivity for the urinary bladder (about 30-fold) compared with the parotid gland. The present data obtained in two human tissues that are highly cholinergic in their innervation give support to the argument for heterogeneity of the muscarinic cholinergic receptors.