Differential distribution of muscarinic receptor subtypes and their regulation by G-protein in rat brain

Abstract

1. [ 3H]quinuclidinyl benzilate ([ 3H]QNB) binding in rat cerebral and cerebellar synaptosomes had different B max values, but similar K d values. 2. These bindings could be displaced by classic muscarinic agents: pilocarpine (partial agonist), and atropine (antagonist), which both had similar binding affinities in rat cerebral and cerebellar synaptosomes. 3. The new muscarinic M 1 selective agents: McN-A-343 (agonist), prienzepine and trihexyphenidyl (antagonists) and higher affinities for receptor sites in the cerebrum than in the cerebellum. 4. The muscarinic M 2 selective agents: carbachol, oxotremorine (agonists), and AF-DX-116 (antagonist) had higher affinities for receptor sites in the cerebellum than in the cerebrum. 5. GPP(NH)p (40 μM) decreased the binding affinities of carbachol and oxotremorine in the cerebellum, but not in the cerebrum. However, it did not decrease the binding affinities of all the antagonists studied in both brain regions. 6. These results reveal that more muscarinic M 1 sites are present in the cerebrum than in the cerebellum, while the opposite is true for M 2 sites. Furthermore, the regulatory role of G-protein on these muscarinic receptor subtypes in the brain is different.