Age-Related Changes in Cardiac Muscarinic Receptors: Decreased Ability of the Receptor to Form a High Affinity Agonist Binding State

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Abstract
Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (−)−[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3-and 12-monthold animals, 5′;-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16-to 18-fold (p < .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)p induced only a 2.7-fold shift in the carbachol IC50 value (p < .01). The reduced shift was due to an increase in the carbachol IC50 value determined in the absence of Gpp(NH)p (p < .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50, shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.

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