Effect of chronic cholinergic denervation on the m1 muscarinic receptor mechanism.
The first three parts of the transduction mechanism for m1 muscarinic receptors (m1 receptors, receptor-G protein coupling, and the activation of phospholipase C) were studied in the rat hippocampus following unilateral or bilateral surgical lesions of the fimbria/fornix. One nM 3H-pirenzepine was used to label m1 receptors selectively. No changes in m1 receptor numbers were found between age 1.7 and 29 months old during normal aging or one year after cholinergic denervation. The interaction between m1 receptors and their associated G protein was examined by competition between 1 nM 3H-pirenzepine and oxotremorine-M in the presence and absence of a guanine nucleotide. The percentage of guanine nucleotide-sensitive high affinity binding sites for the agonist was similar in rats 1.7-29 months old and in rats 1 year after denervation. The ability of oxotremorine-M to activate phospholipase C, via m1, m3, and m5 receptors was also unchanged more than a year after cholinergic denervation of the hippocampus. We concluded that the initial steps in the m1 receptor transduction mechanism remain remarkably stable after denervation.
Pearce
B D
BD
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, FL 33101.
Liskowsky
D R
DR
Potter
L T
LT
D000110:Acetylcholinesterase / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D001345:Autoradiography; D003714:Denervation; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology; D006868:Hydrolysis; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000187:drug effects*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D000110:Acetylcholinesterase