Alpha₁- and Beta-Adrenergic Receptors in Myocardial Ischemia and Injury

Abstract

Cell surface receptors of hormones and neurotransmitters are dynamic entities whose expression is altered in a variety of settings. Adrenergic receptor expression, as for other classes of such cell surface receptors, most likely represents the interplay of cellular processes involved in receptor synthesis, intracellular transport and membrane insertion, internalization recycling, and degradation (the receptor “life cycle” [1, 2]). Several years ago, we began studies designed to decipher events in the life cycle of cardiac α₁- and β-adrenergic receptors that might be altered by myocardial ischemia. Ischemia produces dramatic effects on the myocardium, probably including increased arrhythmogenic and other responses to catecholamines [3–6]. When we began our work, we hypothesized that redistribution of cellular pools of adrenergic receptors in myocardial cells might explain the observations of increases in adrenergic receptors in crude membranes prepared from ischemic hearts and that such redistribution might contribute to the increased response of the heart to catecholamines in ischemia [3–7]. In this article, will review some of our observations [8–10] that appear to confirm this hypothesis. We will also present other results that represent a further extension of this hypothesis and that suggest a mechanism for the beneficial effects of β-adrenergic antagonists in ischemic heart disease.