Muscarinic receptor binding is inhibited by quinacrine.
Quinacrine altered the equilibrium binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to the muscarinic receptor in membranes from N18TG2 neuroblastoma cells. At 1 microM quinacrine, the apparent Kd for [3H]QNB binding was shifted from 48 to 210 pM without a decrease in the maximum binding. The competition binding profile of quinacrine indicates that it displaced [3H]QNB binding with an IC50 of 460 nM in a manner consistent with competitive inhibition. Quinacrine blocked the muscarinic inhibition of cyclic AMP accumulation by carbachol in cultured N18TG2 neuroblastoma cells without affecting arachidonic acid release or Gi coupling to the adenylate cyclase. The disruption of muscarinic receptor function by quinacrine may provide an explanation for its blockade of the muscarinic response in cells.
O'Donnell
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Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, MO 63104.
Howlett
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D001667:Binding, Competitive; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D018727:Muscarinic Antagonists; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D011796:Quinacrine / Q000378:metabolism / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D012633:Secretin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012633:Secretin; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D000242:Cyclic AMP; D011796:Quinacrine; D002118:Calcium