α2BAdrenergic receptor 301-303 deletion polymorphism and vascular α2adrenergic receptor response

Mordechai Muszkat, Gbenga G. Sofowora, Hong Guang Xie, Alastair J.J. Wood, C. Michael Stein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Postsynaptic α2Badrenergic receptors (ARs) mediate vasoconstriction. There is more than 1000-fold variability in vascular sensitivity to an α2-AR agonist. Genetic variability may contribute to such interindividual differences in sensitivity. A 301-303 deletion (del) polymorphism has been identified in the coding region of the α2B-AR gene and has functional effects in vitro. Thus, we examined the hypothesis that the del301-303 polymorphism contributes to variability in vascular α2-AR responses in vivo. Healthy subjects were recruited based on their α2B-AR genotype. Their vascular sensitivity was determined using a linear variable differential transformer following the infusion of increasing doses (range 0.01-1000 ng/min) of the α2-AR agonist, dexmedetomidine, into a dorsal hand vein. The dose that produced 50% (ED50) of maximum venoconstriction (Emax) was determined for each subject. Vascular response was compared among the three genotypes. Forty-nine subjects were studied [28 wild-type wt/wt, 13 wt/del, 8 del/del]. There was no difference in dexmedetomidine ED50and Emaxamong the α2B-AR del301-303 genotypes. The ED50was 1.39 ng/min [95% confidence interval (CI) 0.03-63.0 ng/min] in wt/wt subjects, 1.63 ng/min (95% CI 0.01-177.8 ng/min) in wt/del and 2.37 ng/min (95% CI 0.17-33.7 ng/min) in del/del (P =0.80). The average Emaxwas 75.4±14.9% in wt/wt, 75.7±21.3% in wt/del and 82.2±12.9% in del/del subjects (P =0.26). These findings suggest that the del301-303 polymorphism does not contribute significantly to interindividual in vivo variability in response to α2-AR activation in the hand vein.

Original languageAmerican English
Pages (from-to)23-28
Number of pages6
JournalPharmacogenetics and Genomics
Volume15
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Keywords

  • adrenergic alpha receptor
  • adrenergic receptor agonists
  • human
  • vasoconstriction
  • veins
  • α301-303 deletion polymorphism

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