P Adrenergic receptor subtypes

Devic E, Xiang Y, Gould D, Kobilka B. P-adrenergic receptor subtype-specific signaling in cardiac myocytes from p, and P2 adrenoceptor knockout mice. Mol Pharmacol 2001 60 577-583. 

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

Chruscinski A, Brede ME, Meinel L, Lohse MJ, Kobilka BK, Hein L. Differential distribution of P-adrenergic receptor subtypes in blood vessels of knockout mice lacking pr or p2-adrenergic receptors. Mol Pharmacol 2001 60 955-962. 

Rybin VO, Xu X, Lisanti MP, Steinberg SF. Differential targeting of P-adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway. J Biol Chem 2000 275 41,447—11,457. 

Steinberg SF. The molecular basis for distinct P-adrenergic receptor subtype actions in cardiomyocytes. Circ Res 1999 85 1101-1 111. 

The distinction between a- and P-adrenergic receptors was first proposed by Ahlquist in 1948 based on experiments with various catecholamine derivatives to produce excitatory (a) or inhibitory (P) responses in isolated smooth muscle systems. Initially, a further subdivision into presynaptic a2- and postsynaptic oq-receptors was proposed. However, this anatomical classification of a-adrenergic recqrtor subtypes was later abandoned. 

Rokosh, D. G. and Simpson, P. C. Knockout of the alpha lA/C-adrenergic receptor subtype the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc. Natl Acad. Sci. U.S.A. 99 9474-9479, 2002. 

Regulation of neurotransmitter receptors the p-adren-ergic receptor. This receptor, of which three subtypes have been cloned, mediates many of the effects of norepinephrine and epinephrine in the brain and peripheral tissues. One of the dramatic features of P-adrenergic receptor function is its rapid desensitization in response to agonist stimulation. It is now known that one important mechanism for this desensitization is phosphorylation of the receptor both by PKA and by a receptor-associated protein kinase, PARK (also called GRK2 Fig. 23-6). 

Cotecchia, S., Rossier, 0., Fanelli, F., Leonardi, A., and De Benedetti, P. G. (2000) The alpha la and alpha lb-adrenergic receptor subtypes molecular mechanisms of receptor activation and of drug action. Pharm. Acta Helv. 74,173-179. 

Hamaguchi, N., True, T.A., Goetz, A.S., Stouffer, M.J., Lybrand, T. P. and Jeffs, P.W. (1998) Alpha 1-adrenergic receptor subtype determinants for 4-piperidyl oxazole antagonists. Biochemistry, 37, 5730-5737. 

Norepinephrine is released into the synapse from vesicles [(1) in Fig. 2.7] amphetamine facilitates this release. Norepinephrine acts in the CNS at two different types of noradrenergic receptors, the a and the P [see (2a), (2b) and (3) in Fig. 2.7]. a-Adrenergic receptors can be subdivided into receptors (coupled to phospholipase and located postsynaptically) and tt2 receptors (coupled to Gj and located primarily presynapti-cally) (Insel, 1996). P-Adrenergic receptors in the CNS are predominantly of the P subtype (3 in Fig. 2.7). P receptors are coupled to and lead to an increase in cAMP. Cyclic AMP triggers a variety of events mediated by protein kinases, including phosphorylation of the P receptor itself and regulation of gene expression via phosphorylation of transcription factors. 

In the central nervous system muscarinic acetylcholine receptors are more abundant than nicotinic receptors. They consist of single-chain proteins of mass 70 kDa. They are not ion channels but are 7-helix receptors homologous in sequence with P-adrenergic receptors (Fig. 11-6) and with rhodopsin.648 Five different subtypes (M1-M5) have been characterized. 

Hein P, Michel MC (2007) Signal transduction and regulation are all alphal-adrenergic receptor subtypes created equal Biochem. Pharmacol. 73 1097-1106. 

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. 

The paradigm used by Ahlquist for classifying receptors based on their pharmacological characteristics (i.e., rank order of potency of agonists) was further developed by Lands and colleagues with the subdivision of the P-adrenergic receptors into pr and P2-subtypes (12). The pradrenergic receptor, the dominant receptor in heart and adipose tissue, was equally sensitive to epinephrine and... 

Fig. 7. Adrenergic receptor subtypes and their coupled G proteins and effectors. AC, adenylyl cyclase c-AMP, cyclic adenosine-3, 5 -monophosphate DAG, diacylgly-cerol PKA, c-AMP-dependent protein kinase A PKC, protein kinase C PLC-p, phospholipase CP +, activation -, inhibition t, increase i, decrease.

Cotecchia S, Bjorklof K, Rossier O, Stanasila L, Greasley P, Fanelli F. The alb-adrenergic receptor subtype molecular properties and physiological implications. J Recept Signal Transduct Res 2002 22 1-16. 

Muntz KH, Zhao M, Miller JC. Downregulation of myocardial P-adrenergic receptors. Receptor subtype selectivity. Circ Res 1994 74 369-375. 

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. 

Subtype-Specific P-Adrenergic Receptor Signaling in Cultured Cardiac Myocytes... 

Nicholas, A.P., Pieribone, V. and Hokfelt, T. (1993) Distributions of mRNAs for alpha-2 adrenergic receptor subtypes in rat brain An in situ hybridization study. J. Comp. Neurol, 328, 575-594. 

Rokosh, D.G., Stewart, A.F.R., Chang, K.C., Bailey, B.A., Karliner, J.A., Camacho, S.A., Long, C.S., Simpson, P.C., 1996. a,-Adrenergic receptor subtype mRNAs are differentially regulated by a,-adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo. J. Biol. Chem. 271, 5839-5843. 

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