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A common polymorphism in the adenylyl cyclase type 9 (AC9) gene does not alter vascular responses to isoproterenol
Author(s) -
Xie H.,
Landau R.,
Dishy V.,
Sofowora G. G.,
Smiley R. M.,
Kim R. B.,
Wood A. J.,
Stein C. M.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.263
Subject(s) - adenylyl cyclase , agonist , phenylephrine , medicine , endocrinology , vasodilation , stimulation , biology , receptor , ed50 , blood pressure
Adenylyl cyclase (AC) is one of the downstream effectors of β2‐adrenergic receptor (BAR2) stimulation. A common functionally significant polymorphism in the AC9 gene, an A to G substitution at nucleotide 2312, resulting in an Ile to Met at codon 772, has been shown to decrease basal and BAR2‐mediated AC activity and blunt catalytic function in vitro (Small et al., 2003). We hypothesized that the Met772 variant would impair sensitivity to an agonist acting through AC. Venodilation in response to increasing doses of isoproterenol (Iso) (1 ‐ 480 ng/min) infused into a phenylephrine‐preconstricted dorsal hand vein was measured using a linear variable differential transformer. A 66‐fold individual variation was observed in the ED50 for Iso (2.8 – 199.2 ng/min) in 26 healthy women (6 whites and 20 Hispanics, aged 18–42 years). The log ED50 for Iso was not significantly different between the subjects with Ile/Ile ( n =17) and Ile/Met ( n =8) or Met/Met ( n =1) [1.26 ± 0.52 (SD) versus 1.49 ± 0.56; P = 0.31]. No differences in the Emax for Iso were observed (101.3% ± 11.8 versus 102.6% ± 13.7; P = 0.80). These findings suggest that the Met772 variant of AC9 is not a major determinant of variability in vasodilatory response to a BAR2 agonist. Clinical Pharmacology & Therapeutics (2004) 75 , P70–P70; doi: 10.1016/j.clpt.2003.11.263