Competitive inhibition of phosphoinositide hydrolysis by the muscarinic receptor antagonist AF-DX 116 is of low affinity in mouse cerebral cortex.
Carbamylcholine stimulated [3H]inositol phosphate accumulation in mouse cerebral cortical slices with an ED50 value of approximately 70 microM. Increasing concentrations of the M2 selective muscarinic cholinergic receptor antagonist, AF-DX 116 (0.3-3.0 microM). produced parallel shifts to the right for concentration-response curves to carbamylcholine. A pA2 value for AF-DX 116 of 6.5 (low affinity) was obtained from Schild plot analysis. It is concluded that the M2 muscarinic receptor subtype, as defined by high affinity [3H]AF-DX 116 radioligand binding, is not appreciably coupled to polyphosphoinositide hydrolysis in the mouse cerebral cortex.
Smith
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TL
Veterans Administration Medical Center, Tucson, AZ 85723.
Yamamura
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HI
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013403:Sugar Phosphates / Q000493:pharmacokinetics*
D007295:Inositol Phosphates; D011976:Receptors, Muscarinic; D013403:Sugar Phosphates; D010890:Pirenzepine; D002217:Carbachol; C048593:otenzepad