Regulatory Role of Magnesium Ion and Guanosine-5'-Triphosphate on Binding of Muscarinic Agonists to the Bovine Tracheal Smooth Muscle Preparation

鎂離子與GUANOSINE-5'-TRIPHOSPHATE對牛氣管平滑肌標本蕈毒素作用劑結合的調節作用

程斌(J. B. Cheng) ； 張正廣(T. K. Chang) ； 張佩珍(P. J. Chang)

《The Chinese Journal of Physiology》 26卷1期 (1983/06) Pp. 49-60

摘要

為了解鎂離子與quanosine-5'-Triphosphate(GTP)對呼吸道蕈毒素作用劑之調節作用，我們分析它們對牛氣管標本oxotremorine（或methacholine/((上標 3)H)quinuclidinyl benzilate(QNB)與oxotremorine/((上標 3)H)oxotremorine(OT)競爭曲線的影響。發現鎂離子顯著地增加2.2×10^(-8)-4.7×10^(-6)M oxotremorine對呼吸道((上標 3)H)QNB結合之抑制作用，但却不改變oxotremorine對((上標 3)H)QNB在低親合力結合區之競爭能力，同樣地，鎂離子使methacholine競爭曲線向左移動，然而同標本中GTP明顯減低methacholine對((上標 3)H)QNB結合之抑制作用。進一步分析oxotremorine/(3H)OT競爭曲線顯示鎂離子誘引其曲線向左移動，此發現與其對作用劑/((上標 3)H)QNB曲線結果相吻合。我們證實鎂離子誘引增加高親合力作用劑結合是非常靈敏（ED50=18 μM），單價陽離子並不具類似的作用。此些結果與鎂離子引出呼吸道一非常高親合力作用劑接合區之見解是一致的。我們建議鎂離子對此形成之影響具有生理顯著性並提出一模式系統解釋鎂離子與GTP如何調節呼吸道蕈毒素作用劑結合區之親合力。

並列摘要

To understand the regulation of Mg(superscript 2+)and guanosine-5'-triphosphate(GTP) on airway muscarinic agonist binding, we have analyzed their effects on the competition curves of oxotremorine (or methacholine)/((superscript 3)H)quinuclidinyl benzilate(QNB)and oxotremorine/((superscript 3)H)oxotremorine(OT) in a bovine tracheal muscle preparation. We found that Mg(superscript 2+)significantly increased the inhibition of 2.2×10^(-8)-4.7×10^(-6)M oxotremorine on airway((superscript 3)H)QNB binding, whereas it did not change the ability of oxotremorine to compete with((superscript 3)H)QNB for an agonist low affinity site. Similarly, Mg(superscript 2+)shifted the methacholine competition curve to the left. However, GTP apparently decreased the inhibition of methacholine on((superscript 3)H)QNB bindingin the same preparation.Further analysis of the oxotremorine/((superscript 3)H)OT competition curve indicates a Mg(superscript 2+)induced leftward shift of the curve, a finding consistent with its effect on the agonist/((superscript 3)H)QNB curves. We demonstated that Mg(superscript 2+)-induced increase in agonist binding to the high affinity site is very sensitive(ED50±18 μM) and the monovalent cation could not mimic its effect. These results are compatible with the hypothesis that Mg(superscript 2+) induces formation of a very high affinity binding site in airways. We suggest a physiological importance of the Mg(superscript 2+) effect on such formation, and propose a model system explaining how Mg(superscript 2+) and GTP regulate affinities of airway muscarinic agonist binding sites.

並列關鍵字

Mg(superscript 2+) ； GTP ； Agonist binding ； Muscarinic receptor ； Tracheal smooth muscle