PC12 phaeochromocytoma cells contain an atypical muscarinic receptor binding site.

Abstract

1. Kinetic, saturation and competition binding studies were conducted on the muscarinic receptor binding site labelled by [3H]-N-methylscopolamine [( 3H]-NMS) in intact PC12 cells and cell membranes. Similar studies were conducted on M1 receptors of rat cortex labelled with [3H]-pirenzepine and M2 and M3 receptors present in rat heart and submaxillary gland respectively, and labelled with [3H]-NMS. 2. The dissociation of [3H]-NMS from muscarinic receptors in PC12 cells was slower than dissociation from both M2 and M3 muscarinic receptors. 3. The Kd of [3H]-NMS in the PC12 cells was significantly lower than that obtained at the M2 and M3 receptor. 4. In competition studies the affinity data for pirenzepine, hexahydroadiphenine and 4-diphenylacetoxy-N-methylpiperidine methiodide were consistent with the presence of an M3 receptor in the PC12 cells. However, for AF-DX 116, cyclohexylphenyl(2-piperidinoethyl)silanol and methoctramine affinity estimates in PC12 cells were 3-6 fold lower than at the M3 receptor. 5. On the basis of these data we conclude that the muscarinic receptor present in the PC12 cells differs from the M1, M2 and M3 subtypes already described.