REVIEW In general, alpha1-adrenergic receptors mediate contraction and hypertrophic growth of smooth muscle cells. alpha1-Receptors are 7-transmembrane domain receptors coupled to G proteins, Gq/11. Three alpha1-receptor subtypes, which share approximately 75% homology in their transmembrane domains, have been identified: alpha1A (chromosome 8), alpha1B (chromosome 5), and alpha1D (chromosome 20). Terazosin is the first alpha1-receptor antagonist to demonstrate selectivity for the alpha1A-receptor. All three receptor subtypes appear to be involved in maintaining vascular tone. The alpha1A-receptor maintains basal vascular tone while the alpha1B-receptor mediates the vasocontrictory effects of exogenous alpha1-agonists. Activation of alpha1-receptors activates Gq-proteins, which results in intracellular stimulation of phospholipases C, A2, and D. This results in mobilization of Ca2+ from intracellular stores, activation of mitogen-activated kinase and PI3 kinase pathways and subsequent vasoconstriction. Terozosin produces its pharmacological effects by inhibiting alpha1A-receptor activation. Inhibition of these receptors in the vasculature and prostate results in muscle relaxation, decreased blood pressure and improved urinary outflow in symptomatic benign prostatic hyperplasia.
REFERENCES
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Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404.
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