کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9921463 | 1559223 | 2005 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A “locked-on,” constitutively active mutant of the adenosine A1 receptor
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
We studied the wild-type human adenosine A1 receptor and three mutant receptors, in which the glycine at position 14 had been changed into an alanine, a leucine, or a threonine residue. All receptors were characterized in radioligand binding experiments, the wild-type and the Gly14Thr mutant receptor in greater detail. Both receptors were allosterically modulated by sodium ions and PD81,723 (2-amino-4,5-dimethyl-3-thienyl-[3(trifluoromethyl)-phenyl]methanone), although in a different way. All mutant receptors appeared to be spontaneously or “constitutively” active in a [35S]GTPγS binding assay, the first demonstration of the existence of such CAM (constitutively active mutant) receptors for the adenosine A1 receptor. The Gly14Thr mutant receptor was also constitutively active in another functional assay, i.e., the inhibition of forskolin-induced cAMP production in intact cells. Importantly, this mutant displayed a peculiar “locked-on” phenotype, i.e., neither agonist nor inverse agonist was capable of modulating the basal activity in both the GTPγS and the cAMP assay, unlike the wild-type and the two other mutant receptors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 510, Issues 1â2, 7 March 2005, Pages 1-8
Journal: European Journal of Pharmacology - Volume 510, Issues 1â2, 7 March 2005, Pages 1-8
نویسندگان
Rianne A.F. de Ligt, Scott A. Rivkees, Anna Lorenzen, Rob Leurs, Ad P. IJzerman,