The differential loss of [3H]pirenzepine vs [3H] (-) quinuclidinylbenzilate binding to soluble rat brain muscarinic receptors indicates that pirenzepine binds to an allosteric state of the muscarinic receptor.
[3H]Pirenzepine [( 3H]PZ) and [3H] (-)Quinuclidinylbenzilate [( 3H] (-)QNB) specific binding to soluble rat brain muscarinic cholinergic receptors was assessed as a function of time subsequent to receptor solubilization. The soluble brain muscarinic receptor is stable at 4 degrees C when assayed by [3H] (-)QNB binding (t 1/2 = 80 hrs). In contrast the pirenzepine state of the receptor decays rapidly (t 1/2 = 3.0 hrs). Prior occupation of the receptor with [3H] (-)QNB or [3H]PZ increases the receptor stability by two to five fold (t 1/2 QNB greater than 1,000 hrs; t 1/2 PZ = 6.5 hrs). These data indicate that pirenzepine binds to an allosteric state of the muscarinic receptor and that caution should be employed in the assignment of receptor subtypes based solely upon the binding of ligands which recognize unique conformational states.
D000495:Allosteric Site; D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004355:Drug Stability; D006207:Half-Life; D010890:Pirenzepine; D011487:Protein Conformation; D011812:Quinuclidines / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*
D001570:Benzodiazepinones; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate