Possible allosteric interaction of 4-aminopyridine with rat brain muscarinic acetylcholine receptors.
The interaction of the potassium channel blocker 4-aminopyridine (4-AP) and its analogs with muscarinic acetylcholine receptors was studied in rat brain homogenate. 4-AP displaced specific [3H]quinuclidinyl benzilate [( 3H]QNB) binding in a concentration-dependent fashion. Hill coefficient values decreased with increasing the concentration of [3H]QNB and different analogs of 4-AP demonstrated varying potencies. Scatchard analysis of saturation isotherms of specific [3H]QNB binding showed that low concentrations of 4-AP slightly reduced maximum binding without affecting the equilibrium dissociation constant, whereas higher concentrations reduced maximum binding further and significantly increased the equilibrium dissociation constant. Schild plots of these data resulted in curvilinear functions. The results are discussed in terms of possible allosteric interactions between potassium channels and muscarinic receptor binding sites.
Lai
W S
WS
Ramkumar
V
V
el-Fakahany
E E
EE
D015761:4-Aminopyridine; D000495:Allosteric Site; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D005260:Female; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014316:Tritium
D000631:Aminopyridines; D007473:Ion Channels; D009467:Neuromuscular Depolarizing Agents; D011976:Receptors, Muscarinic; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D015761:4-Aminopyridine; D011188:Potassium