Modulation of receptor sensitivity: possible therapeutic target?
Ischaemic preconditioning and post-conditioning are cardioprotective interventions that salvage ischaemic myocardium and reduce infarct size. Yet this cardioprotective effect is not the sole response of the heart to ischaemic preconditioning and post-conditioning. It was known that protein kinase C activation in the signalling cascade of ischaemic preconditioning increased the affinity of the adenosine A(2b) receptor so that much lower concentrations of adenosine caused A(2b) receptor-dependent signalling. In this issue of the British Journal of Pharmacology, these cardioprotective interventions are shown to block desensitization of surface receptors on the sarcolemma of the cardiomyocyte and this receptor effect is divorced from any cardioprotection. Modulating receptor function through signalling pathways is a novel idea but, currently, whether these observations have any clinical relevance is not known. Additional investigations are warranted to determine whether this effect on receptors can be generalized to other surface receptors, and whether the effect can be harnessed to improve treatment of the patient with acute myocardial infarction.
Department of Physiology, University of South Alabama, College of Medicine, Mobile, AL 36688, USA. mcohen@usouthal.edu
Michel V
MV
Cohen
James M
JM
Downey
D000818:Animals; D004789:Enzyme Activation; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D044162:Parathyroid Hormone-Related Protein; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D044168:Receptor, Parathyroid Hormone, Type 1; D011943:Receptors, Adrenergic, beta