Pirenzepine indicates heterogeneity of muscarinic receptors linked to cerebral inositol phospholipid metabolism.

Muscarinic receptor-mediated inositol phospholipid metabolism was examined in rat cerebral cortex and medulla-pons slices prelabelled with 3H-inositol. Carbachol stimulated accumulation of 3H-inositol phosphate in both regions with identical EC50 values though the maximal stimulation was considerably greater in cortex. The carbachol response was potently suppressed by atropine with very similar affinities in both regions. However, the M1 antagonist pirenzepine displayed a 10-fold greater affinity for the cortical carbachol response. The data supports the concept of heterogeneity of cerebral muscarinic receptors and suggests that both M1 and M2 sites may be linked to inositol phospholipid metabolism in brain.