Cachelin A B, Rust G
Department of Pharmacology, University of Berne, Switzerland.
Pflugers Arch. 1995 Jan;429(3):449-51. doi: 10.1007/BF00374164.
We have investigated the effect of 4 ganglionic cholinergic antagonists (hexamethonium, mecamylamine, pentolinium, trimetaphan) on rat alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. Current responses were elicited by fast application of acetylcholine on voltage-clamped oocytes (holding potentialVh = -80mV). Concentration-inhibition curves were used to get estimates of IC50, the antagonist concentration yielding 50% reduction of the peak current. The KB's of the antagonists were calculated using estimates of the apparent KD of acetylcholine. The order of affinity of the antagonists was similar for both receptor subtypes: mecamylamine approximately pentolinium > hexamethonium > trimetaphan. However, alpha 3 beta 4 neuronal nAChRs were 9 to 22 times more sensitive to each of the 4 antagonists than alpha 3 beta 2 receptors. These results further underline the importance of the beta-subunit as co-determinant of the functional properties of neuronal nAChRs.
我们研究了4种神经节胆碱能拮抗剂（六甲铵、美加明、喷托铵、阿方那特）对非洲爪蟾卵母细胞中表达的大鼠α3β2和α3β4神经元烟碱型乙酰胆碱受体（nAChRs）的作用。通过在电压钳制的卵母细胞（钳制电位Vh = -80mV）上快速施加乙酰胆碱来引发电流反应。利用浓度-抑制曲线来估算IC50，即导致峰值电流降低50%的拮抗剂浓度。使用乙酰胆碱表观KD的估算值来计算拮抗剂的KB值。两种受体亚型的拮抗剂亲和力顺序相似：美加明≈喷托铵＞六甲铵＞阿方那特。然而，α3β4神经元nAChRs对这4种拮抗剂中的每一种的敏感性都比α3β2受体高9至22倍。这些结果进一步强调了β亚基作为神经元nAChRs功能特性共同决定因素的重要性。
