Evidence for the coupling of muscarinic M1 receptors to polyphosphoinositide turnover in rat cortical synaptosomes.
The linking event between the activation of muscarinic M1 receptors and the stimulation of polyphosphoinositide (PPI) turnover was studied in rat brain synaptosomes from the muscarinic M1 enriched cerebrum and M2 enriched cerebellum. The muscarinic M1 selective antagonists, pirenzepine and trihexyphenidyl, and M2 selective antagonist AF-DX-116 were chosen to displace the non-selective labeled cholinergic ligand, 3H-QNB, binding to these two regions of the brain synaptosomes. The IC50 values obtained for these agents revealed a typical characterization of the receptor subtypes of these two regions as they are. Carbachol-induced a stimulation of the PPI turnover cycle: namely, a decrease in 32Pi incorporation into phosphatidylinositol-4,5-bisphosphate (TPI) and phosphatidylinositol-4-phosphate (DPI), and an increase in this incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA) in rat brain synaptosomes from the cerebrum. However, this event was only barely detectable in the synaptosomes from the cerebellum. The IC50 values obtained for these antagonists to block the carbachol-induced PPI turnover cycle in the synaptosomes from the cerebrum were close to the values obtained for the displacement of 3H-QNB binding to the same preparation, and were far away from those values obtained in the synaptosomes from the cerebellum. Our results suggest that there is evidence to support the view that muscarinic M1 receptors are coupled to the PPI turnover event in rat cortical synaptosomes.
Wei
J W
JW
Institute of Neurosciences, National Yang-Ming Medical College Taipei, Taiwan, Republic of China.
Hung
W C
WC
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010890:Pirenzepine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D014282:Trihexyphenidyl / Q000494:pharmacology
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D014282:Trihexyphenidyl; D002217:Carbachol