3-Adrenergic receptors subtypes, roles

Wang RX, Limbird LE (1997) Distribution of mRNA encoding three a2-adrenergic receptor subtypes in the developing mouse embryo suggest a role for the U2a subtype in apoptosis. Mol Pharmacol 52 1071-1080... 

DeGraff JL, Gagnon AW, Benovic JL, Orsini MJ. Role of arrestins in endocytosis and signaling of oq-adrenergic receptor subtypes. J Biol Chem 1999 274 11,253-11,259. 

Role of p-Adrenergic Receptor Subtypes in Regulating Cardiac Function... 

Polymorphisms have been described for all (3-adrenergic receptors while initial studies, notably of the (3i-subtype, suggested that these might be predictors of diseases as well as of therapeutic responses, these results have more recently been questioned. Alterations in responsiveness may be limited to certain compounds and a causative role in diseases has not been or remains to be substantiated in larger trials. 

Beta-1, beta-2, and beta-3 adrenergic receptors are G-protein-coupled receptors. Beta-1 and beta-2 receptors mediate the positive inotropic, chronotropic, and dro-motropic effects of the endogenous catecholamines epinephrine and norepinephrine. The beta-3 subtype seems to play a role in regulating thermogenesis and lipid mobilization in brown and white adipose tissue. Several coding and promoter polymorphisms of these receptors have been identified. Clinical studies in asthma... 

Lakhlani, P.P., MacMillan, L.B., Guo, T.Z., McCool, B.A., Lovinger, D.M., Maze, M., and Limbird, L.E. (1997) Substitution of a mutant ajA-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci USA 94 9950-9955. 

Shizukuda, Y., and Buttrick, P.M. 2002. Subtype specific roles of P-adrenergic receptors in apoptosis of adult rat ventricular myocytes. J. Mol. Cell. Cardiol. 34 823-831. 

Mice lacking the oqB-adrenergic receptor were generated by the Cotecchia lab in 1997 (76). Whereas basal blood pressure was not altered in these animals, the hypertensive response to oq-agonists was significantly blunted. Subsequently, the a1A- (77) and a1D-knockouts (78) were generated. All three oq-subtypes play important roles in the cardiovascular system, and the oqB may be particularly important in the central nervous system (reviewed in ref. 79) (see Chapter 8). 

The a2B-Adrenergic Receptor Null Mice Reveal Roles for the a2B-AR Subtype in Hypertension, Antinociception to Nitrous Oxide, and Development 3.1. The a2B-AR in Blood Pressure Regulation... 

P-Adrenergic receptors ((i-ARs) are members of the superfamily of G protein-coupled receptors that are stimulated by the catecholamines epinephrine and norepinephine (1). As part of the sympathetic nervous system, P-ARs have important roles in cardiovascular, respiratory, metabolic, central nervous system, and reproductive functions. Mice lacking one or more of the three p-AR subtype genes (P, p2, and p3) have been generated to elucidate the physiological role of individual subtypes. Moreover, cells and tissues extracted from these mice have been utilized as tools to understand the molecular and cellular basis of subtype-specific receptor function. These studies are summarized in this chapter. 

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