Sethy_1990_Neuropharmacol_29_185

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.