Asymmetric distribution and down-regulation of the muscarinic acetylcholine receptor in rat cerebral cortex.

The distribution and down-regulation of the muscarinic acetylcholine receptor (mAChR) were studied in dissociated cells from right (RCC) and left (LCC) cerebral cortex. For this purpose [3H]quinuclidinyl benzilate (QNB) and [3H]pirenzepine (Pz), two muscarinic antagonists, were used. The mAChR binding sites detected with [3H]QNB were asymmetrically distributed between the two hemispheres, the majority being found in the RCC. Asymmetry was also evident in the distribution of the mAChR subtypes (M1 and M2) detected with [3H]Pz. Under basal conditions the RCC had roughly 50% more M1 subtype than the LCC. The pharmacological and kinetic parameters were similar for both antagonists in RCC and LCC, indicating that the observed lateralization was due to a different density of the receptor rather than to different kinetics of binding of the two radioligands. After sustained stimulation with the agonist carbamoylcholine, the receptor sites detected with [3H]Pz, i.e. the M1 subtype of mAChR, decreased at a higher rate in the RCC (44%) than in the LCC (25% of controls), demonstrating that the down-regulation process is more active in the right than in the left cortex, and thus implying that there is better coupling between the stimulated mAChR and its effector system in the former.