کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2515592 1118534 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Role of the second transmembrane domain of rat adenosine A1 receptor in ligand–receptor interaction
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Role of the second transmembrane domain of rat adenosine A1 receptor in ligand–receptor interaction
چکیده انگلیسی

Initial mutagenesis studies exploring the ligand recognition model of A1 adenosine receptor (A1R) mainly focused on the residues in the 5th–7th transmembrane domains (TMs5–7). Little is known about the role of residues in TM2. To explore the importance of reserved hydrophobic region in TM2 of A1R, we mutated the hydrophobic residues at positions 65 and 69 to hydrophilic residues (L65T, Leu-65 to Thr-65; I69T, Ile-69 to Thr-69; I69S, Ile-69 to Ser-69) to change the hydrophobicity at the outer end of TM2. Binding assays showed that the affinities of mutant receptors were significantly decreased for ribose group-containing agonists (2-chloro-N6-cyclopentyladenosine (CCPA) and 5′-N-ethyl-carboxamidoadenosine (NECA)) but not for antagonists, N6-cyclopentyl-9-methyladenine (N-0840), an adenine derivative lacking ribose group, and 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX), a xanthine derivative. This observation suggests that the hydrophobic region at the outer end of TM2 may mediate the recognition of the ribose group of CCPA and NECA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 71, Issue 6, 14 March 2006, Pages 865–871
نویسندگان
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