EFFECT OF CHRONIC CHOLINERGIC DENERVATION ON THE M1 MUSCARINIC RECEPTOR MECHANISM

The first three parts of the transduction mechanism for m l muscarinic receptors (m l receptors, receptor-G protein coupling, and the activa tion of phospholipase C) were studied in the rat hippocampus following unilateral or bilateral surgical lesions of the fimbria/fornix. One n M H-3-pirenzepine was used to label m l receptors selectively. No chan ges in m l receptor numbers were found between age 1.7 and 29 months o ld during normal aging or one year after cholinergic denervation. The interaction between m l receptors and their associated G protein was e xamined by competition between 1 nM H-3-pirenzepine and oxotremorine-M in the presence and absence of a guanine nucleotide. The percentage o f guanine nucleotide-sensitive high affinity binding sites for the ago nist was similar in rats 1.7-29 months old and in rats 1 year after de nervation. The ability of oxotremorine-M to activate phospholipase C, via m l, m3, and m5 receptors was also unchanged more than a year afte r cholinergic denervation of the hippocampus. We concluded that the in itial steps in the m l receptor transduction mechanism remain remarkab ly stable after denervation.