Hejnová L, Tucek S, el-Fakahany E E
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Eur J Pharmacol. 1995 Nov 30;291(3):427-30. doi: 10.1016/0922-4106(95)90085-3.
It was previously found that alcuronium increases the binding of [3H]methyl-N-scopolamine to cardiac muscarinic receptors by a positive allosteric action while its effect on the binding of [3H]quinuclidinyl benzilate is negative. The, features of the antagonist's molecule which decide whether its allosteric interaction with alcuronium is positive or negative are not known. In the present work, it was found that alcuronium has a positive allosteric effect also on the binding of [3H]atropine and [3H]methyl-N-piperidinyl benzilate to muscarinic receptors in rat heart atria and that its effect on the binding of [3H]methyl-N-quinuclidinyl benzilate is negative. A comparison of the five radiolabelled antagonists that have been investigated so far indicates that the type of allosteric interaction (positive or negative) is not determined by the presence or absence of the quaternary nitrogen or of the benzilyl moiety in the molecule of the antagonist. Apparently, features of the N-bearing moiety of muscarinic antagonists other than the presence of a charge on nitrogen play a key role in the determination of the type of interaction.
先前发现，阿库氯铵通过正变构作用增加[3H]甲基-N-东莨菪碱与心脏毒蕈碱受体的结合，而其对[3H]喹核醇基苯甲酸酯结合的影响则为负性。决定其与阿库氯铵变构相互作用是正性还是负性的拮抗剂分子特征尚不清楚。在本研究中，发现阿库氯铵对[3H]阿托品和[3H]甲基-N-哌啶基苯甲酸酯与大鼠心房毒蕈碱受体的结合也有正变构效应，而其对[3H]甲基-N-喹核醇基苯甲酸酯结合的影响为负性。对目前已研究的五种放射性标记拮抗剂的比较表明，变构相互作用的类型（正性或负性）并非由拮抗剂分子中是否存在季铵氮或苯甲酰基部分所决定。显然，毒蕈碱拮抗剂含氮部分的特征（而非氮上的电荷）在决定相互作用类型方面起关键作用。
