Evidence for the Coupling of Muscarinic M1 Receptors to Polyphosphoinositide Turnover in Rat Cortical Synaptosomes

活化大白鼠大腦皮質突觸體香草素M1亞型受體可促進多磷脂醯肌醇的轉變反應

魏健吾(Jiann-Wu Wei) ； 洪文俊(Wen-Chun Hung)

《The Chinese Journal of Physiology》 32卷2期 (1989/12) Pp. 103-114

摘要

本研究係利用大白鼠腦部富有M1亞型受體之大腦皮質及富有M2亞型受體之小腦皮質製作成突觸體，以探討活化香蕈素亞型受體與促進多磷脂醯肌醇轉變兩者之間的關係。具有選擇作用於M1型受體拮抗劑：pirenzepine和trihexyphenidy1及M2亞型受體拮抗劑：AF-DX-116等藥物，被使用於取代放射標識物：(上標 3)H-QNB（一種非選擇性之香蕈素型受體拮抗劑）與腦部香蕈素型受體之結合反應。由此藥物與受體結合親和力（IC50值：藥物抑制反應50%之劑量）之大小次序，可知大腦及小腦之香蕈素型受體亞型之分布，分別是富有M1及M2型之區域。Carbachol所引發之多磷脂醯肌醇的轉變反應：其結果對於大腦皮質突觸體爲明顯地降低(上標 32)Pi嵌入多磷脂醯肌醇（TPI及DPI），並同時增高(上標 3)H-QNB與大腦皮質M1受體亞型結合之作用程度（IC50值）比較相近，而又與其取代(上標 3)H-QNB與小腦皮質M2受體亞型結合之作用強度（IC50值）相距較遠。由以上結果顯示：大白鼠大腦皮質係含有極多M1受體亞型之區域，而此亞型受體之活化，可促進多磷脂醯肌醇之轉變反應。

並列摘要

Wei, J.W. and W.C. Hung: Evidence for the coupling of muscarinic M1 receptors to polyphos-phoinositide turnover in rat cortical synaptosomes. Chinese J. Physiol. 32(2):103-114, 1989. The linking event between the activation of muscarinic Ml receptors and the stimulation of polyphos-phoinositide (PPI) turnover was studied in rat brain synaptosomes from the muscarinic Ml enriched cerebrum and M2 enriched cerebellum. The muscarinic M1 selective antagonists, pirenzepine and trihexyphenidyl, and M2 selective antagonist AF-DX-116 were chosen to displace the non-selective labeled cholinergic ligand, (superscript 3)H-QNE, binding to these two regions of the brain synaptosomes. The IC50 values obtained for these agents revealed a typical characterization of the receptor subtypes of these two regions as they are. Carbachol-induced a stimulation of the PPI turnover cycle: namely, a decrease in (superscript 32)Pi incorporation into phosphatidylinositol-4, 5-bis- phosphate (TPI) and phosphatidylinositol-4-phosphate (DPI), and an increase in this incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA) in rat brain synaptosomes from the cerebrum. However, this event was only barely detectable in the synaptosomes from the cerebellum. The IC50 values obtained for these antagonists to block the carbachol-induced PPI turnover cycle in the synaptosomes from the cerebrum were close to the values obtained for the displacement of (superscript 3)H-QNB binding to the same preparation, and were far away from those values obtained in the synaptosomes from the cerebellum. Our results suggest that there is evidence to support the view that muscarinic M1 receptors are coupled to the PPI turnover event in rat cortical synaptosomes.

並列關鍵字

muscarinic receptor subtypes ； phosphoinositide turnover ； brain synaptosomes ； (superscript 3)H-QNB binding