Adrenergic receptor classification

Respiratory smooth-muscle cells contain the beta-2 subtype of adrenergic receptors.76 (See Chapter 18 for a discussion of adrenergic receptor classifications.) Stimulation of these beta-2 receptors results in relaxation of bronchiole smooth muscle. Lienee, drugs that stimulate these beta-2 adrenergic receptors (i.e., beta-adrenergic agonists) produce bronchodilation and can be used to prevent or inhibit airway obstruction in bronchospastic diseases.22,99... 

Key Words a,-Adrenergic receptor a2-adrenergic receptor P-adrenergic receptor classification function history molecular cloning pharmacology radioligand binding structure. 

Furchgott, R. F. (1972). The classification of adrenoreceptors (adrenergic receptors) An evaluation from the standpoint of receptor theory. In Handbook of experimental pharmacology, catecholamines, Vol. 33, edited by H. Blaschko and E. Muscholl, pp. 283—335. Springer-Verlag, Berlin. 

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. 

Since there are two primary neurotransmitters involved in autonomic discharge, there are two primary classifications of postsynaptic receptors. Cholinergic receptors are located at acetylcholine synapses, and adrenergic receptors are located at norepinephrine synapses. As indicated in Figure 18-2, each type of receptor has several subclassifications. The location and functional significance of these classifications and subclassifications are presented here. 

While the classification of a-adrenergic receptors into c -and n (ft ). 703 and ft—adranarcric racantors into (5 and 2 subtypes... 

Of the nine adrenergic receptor subtypes, the a1D is the only one to be identified by cloning before characterization pharmacologically. Subsequently, it was shown that the so-called alc-receptor was actually the pharmacological a1A (64,65), and this was formalized by the IUPHAR Adrenergic Receptor Subcommittee (66). The current classification scheme includes the a1A, a1B, and a1D, but there is no alc. A fourth pharmacological subtype, the a1L, has been identified in vascular tissues from several species (67) but may represent a conformational state of the a1A-receptor (68). 

Berthelsen S, Pettinger WA. A functional basis for classification of a-adrenergic receptors. Life Sci 1977 21 595-606. 

Perez DM, Piascik MT, Malik N, Gaivin R, Graham RM. Cloning, expression, and tissue distribution of the rat homolog of the bovine alc-adrenergic receptor provide evidence for its classification as the a1A subtype. Mol Pharmacol 1994 46 823-831. 

Lomasney JW, Cotecchia S, Lefkowitz RJ, Caron MG. Molecular biology of a-adrenergic receptors implications for receptor classification and for structure-function relationships. Biochim Biophys Acta 1991 1095 127-139. 

The discovery of subclasses of adrenergic receptors and the ability of relatively small molecule drugs to stimulate differentially or block these receptors represented a major advance in several areas of pharmacotherapeutics. An excellent review of the development of adrenoceptor classifications is available in Hiebel et al. (47). 

Figure 28-3 Classification and basic architecture of cell-surface receptors that couple to G-proteins. Panel A lists the major families and groups of GPCRs.The mammalian receptors are confined to families A, B, and C. Family A is the largest and includes the diverse odorant receptors and prototypic GPCRs, such as rhodopsin and the p-adrenergic receptor. Panel B shows a schematic structure of one of the most extensively characterized GPCRs, the p-adrenergic receptor. Major structural features are indicated and are expanded on in the text, ffrom Conn PM, Melmed. eds.Textbook of endocrinology.Towanta Nj Humana Press 1997.)...

CLASSIFICATION OF ADRENERGIC RECEPTORS Understanding the diverse effects of the catecholamines and sympathomimetic agents requires understanding the properties of the different types of adrenergic receptors and their distribution on various tissues and organs (Tables 6-1,... 

Understanding the pharmacological properties of sympathomimetics and their antagonists depends on knowledge of the classification, distribution, and mechanism of action of a and fi adrenergic receptors (see Tables 6-1, 6-6, 6-7, Figure 10-1, and Table 10-6). 

FIGURE 10-1 Classification of adrenergic receptor agonists and drugs that produce sympathomimetic effects. For... 

Classification of adrenergic receptor antagonists. Drugs marked by an asterisk ( ) also block... 

Classification of adrenergic receptors Into a and 3 subtypes ( ) Is now generally accepted. On the basis of differences In response to selective agonists (, 5) and antagonists (, 7),... 

StaUaert, W., Dom, J. F., van der Westhuizen, E., Audet, M., Bouvier, M. (2012). Impedance responses reveal beta(2)-adrenergic receptor signahng pluridimensionahty and allow classification of ligands with distinct signahng profiles. PLoS One, 7(1), e29420. http // dx. doi.org/10.1371 /joumal.pone.0029420. 

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