Muscarinic receptor subtypes in respiratory center and their functions

Radioreceptor binding assays using [3H]quinuclidinyl benzilate and [3H]pirenzepine were performed on the pons and medulla oblongata (MeOb) of rat brain. The M1 cholinergic receptor (M1-R) was found to account for approximately 30-40% of the total muscarinic receptors (M-R) in the pons and MeOb, and the M2 accounted for about 60-70%. The receptor binding capacities of scopolamine and atropine were compared with those of pirenzepine (Pir) and AF-DX 116 on the 2 parts of the brain. The affinity values (pKi) suggest that the selectivity of scopolamine for M1-R is greater than for M2-R, and that of atropine for M2 is greater than for M1. In conscious rabbits, the respiratory frequency (FR), tidal volume (TV), and minute ventilation volume (MVV) were determined. Arterial blood samples were taken intermittently and analyzed for pO2, pCO2, and pH. When pilocarpine (a M1-R subtype selective agonist) was given, excitatory effects on respiration were seen through FR, TV, MVV, and the pO2, pCO2, and pH. When 6 beta-acetoxy nortropane (6 beta-AN, a novel M2-R subtype selective agonist) was given, the effects were inhibitory. These results were reversed after administration of Pir, scopolamine, AF-DX 116, and atropine. Thus, it shows that Pir and scopolamine inhibit respiration by blocking the M1-R subtype of the respiratory center, while the excitatory effects of AF-DX 116 and atropine are brought about by blocking the M2-R subtype of the respiratory center.