Functional linkage as a direction for studies in oxidative stress: alpha-adrenergic receptors.
The alpha-adrenergic receptors (adrenoceptors) are activated by the endogenous agonists epinephrine and norepinephrine. They are G protein-coupled receptors that may be broadly classified into alpha1 (subclasses alpha1A, alpha1B, alpha1D) and alpha2 (subclasses alpha2A, alpha2B, alpha2C). The alpha1-adrenoceptors act by binding to G(alpha)q subunits of the G proteins, causing activation of phospholipase C (PLC). PLC converts phosphatidylinositol 4,5-bisphosphate into inositol trisphosphate (IP3) and diacylglycerol (DAG), which have downstream effects on cytosolic Ca2+ concentration. The alpha2-adrenoceptors bind to G(alpha)i thus inhibiting adenylyl cyclase and decreasing cAMP levels. DAG alters protein kinase C activity and cAMP activates protein kinase A. The downstream pathways of the two receptors may also interact. Activation of alpha1- and alpha2-adrenoceptors in vascular smooth muscle results in vasoconstriction. However, the densities of individual receptor subclasses vary between vessel beds or between vessels of various sizes within the same bed. In vasculature, the densities of adrenoceptor subclasses differ between conduit arteries and arterioles. These differences, along with differences in coupling mechanisms, allow for fine regulation of arterial blood flow. This diversity is enhanced by interactions resulting from homo- and heterodimer formation of the receptors, metabolic pathways, and kinases. Reactive oxygen species generated in pathologies may alter alpha1- and alpha2-adrenoceptor cascades, change vascular contractility, or cause remodeling of blood vessels. This review emphasizes the need for understanding the functional linkage between alpha-adrenoceptor subtypes, coupling, cross talk, and oxidative stress in cardiovascular pathologies.
Ziolkowski
Natalia
N
Department of Medicine, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Grover
Ashok K
AK
D000818:Animals; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species; D020239:Receptor Cross-Talk / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology
D017382:Reactive Oxygen Species; D011942:Receptors, Adrenergic, alpha