Differential coupling between muscarinic receptors and G-proteins in regions of the rat brain.
The coupling of muscarinic receptors to G-proteins in various regions of the rat brain was assessed by measuring carbachol-stimulated, low-Km GTPase. The inhibition of carbachol-stimulated GTPase by the M1-selective antagonist pirenzepine was compared to the affinity of pirenzepine for various nuclei within the regions as measured autoradiographically. The rank order of potency of carbachol for stimulating GTPase in various brain regions was similar to that for binding to receptors in those areas. The maximal specific activity (efficacy) of carbachol-stimulated GTPase varied independently of the distribution of total receptors or receptor subtypes. The overall potency of pirenzepine for inhibiting carbachol-stimulated GTPase was not correlated with the overall affinity of pirenzepine for muscarinic receptors in the regions. Comparing results in various brain regions, the data suggest that there are differences in the efficiency of coupling between muscarinic receptors and G-proteins. For example, the pons-medulla appeared to have a small population of pirenzepine-sensitive (M1 or M4) receptors that were coupled very efficiently to G-proteins, whereas in the hippocampus all muscarinic receptors, most of which are pirenzepine-sensitive, appeared to be weakly coupled to G-proteins. It is suggested that variable interactions between receptors and G-proteins may be an important factor in the overall coupling between receptor occupancy and cellular responses to acetylcholine as well as other hormones and transmitters.
Ghodsi-Hovsepian
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Department of Medicinal and Biological Chemistry, University of Toledo, College of Pharmacy, OH 43606.
Messer
W S
WS
Hoss
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W
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010890:Pirenzepine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012249:Rhombencephalon / Q000378:metabolism
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D002217:Carbachol; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins