Effects of age on muscarinic cholinergic receptors in rat myocardium.

Atrial and ventricular myocardium from young (3-4 months old), young adult (7-8 months old), and aged (24-25 months old) rats were used to study the influence of age on cardiac cholinergic muscarinic receptors. The density of muscarinic receptors (expressed as fmol/mg protein or pmol/g tissue), determined by the specific binding of [3H]quinuclidinyl benzylate [( 3H]QNB), was significantly greater (24-29%) in atria of aged rats compared with that in atria of young or young adult rats. The muscarinic receptor density in ventricles was found to be essentially similar in all age groups studied. Antagonist as well as agonist binding characteristics of muscarinic receptor sites were examined in atria and ventricles from young and aged rats. No significant age-related difference was observed in the dissociation constant (KD) of atrial or ventricular receptors for the antagonist ligand [3H]QNB (KD apparent (nM): 1.04 +/- 0.16 and 0.91 +/- 0.12, respectively, for young and aged atria; 0.75 +/- 0.08 and 0.76 +/- 0.10, respectively, for young and aged ventricles). Similarly, the concentrations of muscarinic antagonist atropine and agonist carbachol causing 50% inhibition of [3H]QNB binding to the receptor sites (IC50) in atria and ventricles were not altered by age. Age-related difference was also not evident in the Hill coefficients for [3H]QNB, atropine, and carbachol. These results indicate that diminished responsiveness of the aged heart to vagal stimulation and exogenously administered cholinergic agents reported in the literature cannot be attributed to an age-related reduction in the number of cardiac muscarinic receptors or their affinities toward agonist or antagonist ligands.