Regulation of neocortical muscarinic receptors: effects of drug treatment and lesions

The high affinity and low affinity muscarinic receptors of rat cerebral cortex were studied in various drug-and lesion-induced states by inhibiting the binding of [3H]quinuclidinyl benzilate (QNB) by carbamylcholine. Receptor density and affinity constants were determined by iterative computer fits of data to a noncooperative two-site competitive inhibition model. In control rat cortex, [3H]QNB had an apparent KO of 76 + 7 PM and a B,,, of 229 + 9 pmol/gm, wet weight tissue, while displacement of [3H]QNB by carbamylcholine revealed a high affinity agonist site with a & of 0.6 f 0.1 PM and a low affinity agonist site with a KLI of 66 + 5 PM. In whole cortex, 30 & 2% of the receptors were in the high affinity state. In the frontoparietal cortex, the concentration of agonist high affinity sites correlated with the density of innervation from the nucleus basalis of Meynert (nBM).