RECEPTOR-COUPLED PHOSPHOINOSITIDE HYDROLYSIS IN HUMAN RETINAL-PIGMENT EPITHELIUM

被引:38
作者
FELDMAN, EL
RANDOLPH, AE
JOHNSTON, GC
DELMONTE, MA
GREENE, DA
机构
[1] UNIV MICHIGAN, DEPT OPHTHALMOL, ANN ARBOR, MI 48104 USA
[2] UNIV MICHIGAN, DEPT INTERNAL MED, ANN ARBOR, MI 48104 USA
关键词
D O I
10.1111/j.1471-4159.1991.tb03471.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Carbachol and histamine stimulated phosphoinositide (PPI) hydrolysis in cultured human retinal pigment epithelium (RPE), as reflected by an accumulation of H-3-inositol phosphates in the presence of 10 mM Li+. Carbachol increased PPI hydrolysis to greater than 600% of basal with an EC50 of 60-mu-M; stimulation was linear up to 60 min. This activation likely occurred via the M3 muscarinic cholinergic receptor based on the IC50 values for 4-diphenylacetoxy-N-methylpiperidine methiodide (0.47 nM), pirenzepine (280 nM), and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (1.4-mu-M). Carbachol-mediated PPI hydrolysis was decreased by 80% in the absence of extracellular Ca2+. Histamine stimulated PPI turnover in a linear manner by 180% with an EC50 of 20-mu-M by the H1 histaminergic receptor. Serotonin, glutamate, norepinephrine, and dopamine were inactive. In human RPE, the resting cytoplasmic Ca2+ concentration, as determined by fura-2 fluorescence, was 138 +/- 24 nM. On the addition of carbachol, there was a 180% increase in peak intracellular Ca2+; addition of histamine increased intracellular Ca2+ by 187%. These results suggest receptor-mediated, inositol lipid hydrolysis is coupled to intracellular Ca2+ flux in human RPE.
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页码:2094 / 2100
页数:7
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