title: Effect of irreversible loss of muscarinic receptors on (3H)-acetylcholine release from the hippocampus.
abstract: The role of muscarinic receptors in the regulation of (3H)-acetylcholine (3H-Ach) release from the hippocampus was investigated with the irreversible cholinergic agonist BM-123 (N-[4(2-chloroethylmethylamino)-2-butynyl]2-pyrrolidone). Pretreatment with BM-123 had no significant effect on spontaneous (3H)-Ach release at 12, 24, 72, and 144 hr. However, this treatment significantly reduced the inhibitory effect of oxotremorine (10 microM) on (3H)-Ach release at 12, 24, and 72 hr (p less than 0.02). At these time intervals, there was a significant loss in muscarinic receptors as determined by (3H)-oxotremorine-M binding. The maximum loss of both oxotremorine-induced inhibition of (3H)-Ach release and muscarinic receptors occurred at 12 hr. Both parameters returned to normal by 144 hr. There was a linear relationship between the recovery of (3H)-Ach release and (3H)-oxotremorine-M binding sites. These results indicate that muscarinic receptors play a significant role in the regulation of (3H)-Ach release in hippocampus, and that this receptor system may lack spare receptors.
authors.affiliation: CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
authors.forename: V H
authors.initials: VH
authors.lastname: Sethy
authors.forename: D K
authors.initials: DK
authors.lastname: Hyslop
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010095:Oxotremorine / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D010276:Parasympatholytics; D011760:Pyrrolidinones; D011976:Receptors, Muscarinic; C003025:N-(4-(2-chloroethylmethylamino)-2-butynyl)-2-pyrrolidone; D010095:Oxotremorine; D000109:Acetylcholine