Adrenergic receptor subtypes

There are nine primary adrenergic receptor subtypes 220... 

TABLE 12-5 Properties of human a, adrenergic receptor subtypes... 

TABLE 12-6 Properties of human [5-adrenergic receptor subtypes Pi P2 P3... 

MacMillan, L. B., Hein, L., Smith, M. S., Piascik, M. T. and Limbird, L. E. Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science 273 801-803,1996. 

Heck, D. A. and Bylund, D. B. Differential down-regulation of alpha-2 adrenergic receptor subtypes. Life Sci. 62 1467-1472,1998. 

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. 

Link, R. E., Desai, K., Hein, L. etal. Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science 273 803-805,1996. 

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. 

Hwa, J., Graham, R.M. and Perez, D.M. (1995) Identification of critical determinants of alpha 1-adrenergic receptor subtype selective agonist binding. The Journal of Biological Chemistry, 270, 23189-23195. 

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. 

The best statistical parameters were obtained by correlating the in vivo selectivity with the Vdif descriptor defined with respect to the oqa-AR supermolecule. It is worth noting that the oqa is the adrenergic receptor subtype of functional relevance for the urethra tissue (dog model) [8]. Thus, ligands showing high potency and selectivity for the lower urinary tract are those, which better fit the volume of the supermolecule that represents the binding site of the ala-AR subtype. 

Graham, R.M., Perez, D.M., Hwa, J. and Piascik, M.T. (1996) Alpha 1-adrenergic receptor subtypes. Molecular structure, function, and signaling. Circulation Research, 78, 737-749. 

Rossier, O., Abuin, L., Fanelli, F., Leonardi, A. and Cotecchia, S. (1999) Inverse agonism and neutral antagonism at alpha(la)- and alpha(lb)-adrenergic receptor subtypes. Molecular Pharmacology, 56, 858-866. 

Stanasila, L., Perez, J.B., Vogel, H. and Cotecchia, S. (2003) Oligomerization of the alpha la- and alpha lb-adrenergic receptor subtypes. Potential implications in receptor internalization. The Journal of Biological Chemistry, 278, 40239-40251. 

Bremner, J.B., Coban, B. and Griffith, R. (1996) Pharmacophore development for antagonists at alpha 1 adrenergic receptor subtypes. Journal of Computer-Aided Molecular Design, 10, 545-557. 

Transgenic Models of a2-Adrenergic Receptor Subtype Function... 

Three genes encoding for a2-adrenergic receptor subtypes have been identified from several species, termed a2A. and a2c, respectively (Fig. 1, 2). 

Fig. 2. a2-Adrenergic receptor subtypes. The putative membrane topology of the three mouse a2-receptor subtypes is schematically depicted. Open circles represent amino acids which are identical between all subt es, gray circles represent amino acids which are conserved among two subtypes, dark circles are non-identical amino acids. Tissue distribution of tt2-receptor subtypes is based on mRNA and protein expression references are given in the text... 

Fig. 5. In vivo functions of a2-adrenergic receptor subtypes. This overview assigns physiological effects of a2-receptor stimulation to individual a2-receptor subtypes iDased on experiments performed in transgenic mice carrying deletions in a2-receptor gene (see text for references)...

Eason MG, Jacinto MT, Liggett SB (1994) Contribution of ligand structure to activation of a2-adrenergic receptor subtype coupling to G,. Molec Pharmacol 45 696-702... 

Makaritsis KP, Johns C, Gavras I, Altman JD, Handy DE, Bresnahan MR, Gavras H (1999) Sympathoinhibitory function of the a2A-adrenergic receptor subtype. Hypertension 34 403-407... 

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