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Conservation of the cardiostimulant effects of (–)-norepinephrine across Ser49Gly and Gly389Arg beta₁-adrenergic receptor polymorphisms in human right atrium in vitro

Peter Molenaar, PhD^*,*, Glenn Rabnott, BSc(Hons), Ian Yang, MBBS, FRACP, Kwun M. Fong, MBBS, PhD, FRACP, Santiyagu M. Savarimuthu, MSc, Li Li, MD^*, Malcolm J. West, MBBS, PhD, FRACP^* and Fraser D. Russell, PhD^*

^* National Heart Foundation and Prince Charles Hospital Foundation Cardiovascular Research Centre, Department of Medicine, University of Queensland, Queensland, Australia
Division of Thoracic Medicine, The Prince Charles Hospital, Chermside, Queensland, Australia

View larger version (53K): [in a new window]   Figure 1 Genotyping of the beta1-adrenergic receptor at nucleotide 145 (Ser49Gly) (A) and 1165 (Gly389Arg) (B) in patients undergoing coronary artery bypass grafting from which the right atrium was obtained and used to assess the contractile effects of (–)-norepinephrine at polymorphic beta1-adrenergic receptors. The figure shows polymerase chain reaction fragments of the predicted length after endonuclease digestion to discriminate between patients homozygous for Ser49, Gly49, or heterozygous for Ser49Gly (A) or homozygous for Gly389, Arg389, or heterozygous for Gly389Arg (B). Arg = arginine; bp = base pair; Gly = glycine; Ser = serine.

View larger version (35K): [in a new window]   Figure 2 Concentration-dependent effects of (–)-norepinephrine for changes in contractile force, time to reach peak force, and time to reach 50% relaxation (t50) through activation of Ser49Gly- and Gly389Arg-polymorphisms of the beta1-adrenergic receptor in human right atrium. Contractile force is expressed in terms of absolute force (mN). Experiments were completed by incubation of tissues with 200 µM (–)-isoproterenol to maximally stimulate both beta1- and beta2-adrenergic receptors followed by raising the concentration of Ca2+ to 9.25 mM. Values shown are mean ± SEM, where SEM values were determined from each specific –log (–)-norepinephrine concentration. Errors not shown when smaller than symbol. Values in parenthesis show (tissue number/patient number). Arg = arginine; Gly = glycine; Ser = serine.