Effects of muscarinic agents on cultured human trabecular meshwork cells

被引:22
|
作者
Shade, DL
Clark, AF
Pang, IH
机构
[1] ALCON LABS INC,MOLEC PHARMACOL,FT WORTH,TX 76134
[2] ALCON LABS INC,GLAUCOMA RES,FT WORTH,TX 76101
[3] UNIV N TEXAS,HLTH SCI CTR,DEPT PHARMACOL,FT WORTH,TX
[4] UNIV N TEXAS,HLTH SCI CTR,DEPT ANAT & CELL BIOL,FT WORTH,TX
关键词
human trabecular meshwork cells; muscarinic agents; phospholipase C; intracellular calcium mobilization; M(3) receptors;
D O I
10.1006/exer.1996.0025
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Intracellular calcium measurements were performed in cultured human trabecular meshwork cells preloaded with the cell permeant dye fura 2-AM. Fluctuations in calcium levels were then monitored with microscope-based ratio fluorometry. Carbachol increased intracellular calcium in a dose-dependent manner; as did oxotremorine-M, aceclidine, and pilocarpine. Carbachol's effect was blocked by the non-selective muscarinic antagonist atropine, as well as by muscarinic receptor subtype-selective antagonists such as pirenzepine (M(1)-selective), p-fHHSiD (M(3)-selective), and 4-DAMP (M(1), M(3) subtypes). Rank order of potencies for the antagonists' effects was atropine = 4-DAMP > p-fHHSiD > pirenzepine, a profile suggesting that the M(3) receptor subtype is essential in the carbachol effect. Phospholipase C activity was estimated via measurement of total production of inositol phosphates in cultured human trabecular meshwork cells pre-exposed to H-3-myoinositol. In these cells, carbachol also stimulated phosphoinositide production in a dose-dependent manner, and an antagonist profile similar to that seen for calcium response was obtained when carbachol was used as the effector. The data indicate that muscarinic effects on cultured human trabecular meshwork calcium mobilization and phospholipase C activity are mediated by an M(3)-like receptor subtype. Therefore, the muscarinic M(3) receptor may play a role in trabecular meshwork cell function(s). (C) 1996 Academic Press Limited
引用
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页码:201 / 210
页数:10
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