R. Buscher et al., In-vivo studies do not support a major functional role for the Gly(389)Argbeta(1)-adrenoceptor polymorphism in humans, PHARMACOGEN, 11(3), 2001, pp. 199-205
beta (1)-adrenoceptors play a pivotal role in regulating contractility and
heart: rate in the human heart. Recently, a polymorphism of the beta (1)-ad
renoceptor has been detected: at amino acid position 389 either Gly or Arg
has been found with the Gly(389) exhibiting reduced responsiveness upon ago
nist-induced stimulation in vitro. In order to find out whether the Gly(389
) polymorphism exhibits blunted responsiveness also in vivo we studied, in
healthy volunteers, the effects of exercise on heart rate and heart rate-co
rrected duration of electromechanical systole (QS(2)c as a measure of inotr
opism) which, in humans, is mediated by beta (1)-adrenoceptors stimulation,
Twenty-four healthy volunteers (12 female, 12 male) homozygous for the Gly
(389) or Arg(389) exercised on a bicycle in supine position (25, 50, 75 and
100 W for 5 min each), and heart rate and QS(2)c were assessed; in additio
n, plasma renin activity (PRA) was determined which is also regulated by be
ta (1)-adrenoceptors in humans, Exercise caused work-load dependent increas
es in heart rate and PRE, and shortening of QS(2)c; however, these changes
were not significantly different between the Gly(389) and Arg(389) polymorp
hism Thus, these three beta (1)-adrenoceptor responses did not differ betwe
en volunteers with the Arg(389) versus the Gly(389) polymorphism. Intragrou
p analysis, however, revealed that exercise induced increase in heart rate
and shortening of QS(2)c were higher in female than in male volunteers. In
conclusion our data do not support the idea that the reduced responsiveness
of Gly(389) against agonist-induced stimulation observed in vitro is of ma
jor functional importance in vivo. Pharmacogenetics 11:199-205 (C) 2001 Lip
pincott Williams & Wilkins.