Associate Professor
Peter Molenaar

Biography

Research theme: Health

Research discipline: Pharmacy

Research areas:
Investigation of the molecular properties and physiological significance of different 'states' of the (1-adrenoceptor: (1-Adrenoceptors are proteins that exist in human heart which mediate the cardiostimulant effects of noradrenaline. Some (-blockers, such as (-)-CGP 12177 not only block the receptor but also stimulate it. To accommodate this finding we have proposed that noradrenaline and cardiostimulant (-blockers bind differently to the (1-adrenoceptor. We are investigating: a. the specific features of the (1-adrenoceptor that are critical for activation of the receptor by (-blockers; b. whether activation of the receptor by (-blockers such as (-)-CGP 12177 causes progression of heart failure in an animal model of heart failure and; c. the chemical features of (-blockers that cause the receptor to be activated and not blocked. These studies are likely to lead to the improved design of (-blockers for clinical use. The genetic basis of (-blocker responsiveness in human heart failure: The clinical effect of (-blockers in human heart failure is quite variable. Some patients show marked improvement in heart function whilst others show marginal or no improvement. In patients with non-ischemic cardiomyopathy treated with carvedilol we found that the Arg389Gly-(1-adrenoceptor polymorphism predicts improvement in left ventricular ejection fraction. Investigation of phosphodiesterase enzymes that are responsible for the metabolism of cyclic AMP accumulated by activation of (1- and (2-adrenoceptors in human ventricle: In human heart phosphodisterase enzymes metabolize the cyclic AMP that is increased in response to activation of (-adrenoceptors. These enzymes can be considered to have a protective role against the harmful effects of excessive (-adrenoceptor activation. We are currently investigating the phosphodiesterases that are responsible for metabolism of cyclic AMP raised by activation of (1- and (2-adrenoceptors in human ventricle from patients with end-stage heart failure.

Areas of expertise:

• Human heart research
• G-protein coupled receptors
• Beta-adrenoceptors
• Polymorphisms