Hosey_1981_J.Biol.Chem_256_6395

Quantitative and qualitative differences in muscarinic cholinergic receptors in embryonic and newborn chick hearts have been found in studies using the radioligand [3H]quinuclidinyl benzilate ([3H]QNB) to label the receptors specifically. In both embryonic and newborn hearts, there appears to be a single class of high affinity muscarinic receptors. However, the number of muscarinic receptors/mg of protein in newborn hearts is significantly greater than in embryonic hearts. Homogenates of newborn and 10-day-old embryonic hearts contain 586 and 278 fmol of muscarinic receptors/mg of protein, respectively. The affinities of the muscarinic cholinergic receptor for [3H]QNB in the two preparations are similar; the KD values as estimated from dissociation and association rate constants are 20 and 12 pM for the newborn and embryonic hearts, respectively. In contrast, marked differences in the properties of the receptors in newborn and embryonic hearts were revealed in studies of inhibition of [3H]QNB binding by cholinergic agonists. The cholinergic agonists acetylcholine and carbamylcholine were approximately 10- to 20-fold more potent in inhibiting [3H]-QNB binding to membranes obtained from embryonic hearts as compared to newborn hearts. Thus, there appear to be developmentally related differences in the affinity of the cardiac muscarinic receptor for agonists but not antagonists.