AlA-Adrenergic receptors

GPCR Antitarget Pharmacophore Modeling The ala Adrenergic Receptor 133... 

Fig. 13.3 Common-feature pharmacophores of ala adrenergic receptor antagonists [11], On to each pharmacophore the reference has been mapped, (a) Class I pharmacophore model aligned to prazosin (b) class II pharmacophore model aligned to compound...

CPCR Anti-target Pharmacophore Modeling the ala Adrenergic Receptor 291... 

Zhong H, Murphy TJ, Minneman KP. Activation of signal transducers and activators of transcription by ala-adrenergic receptor stimulation in PC 12 cells. Mol Pharmacol 2000 57 961-967. 

Vazquez-Prado J, Medina LC, Romero-Avila MT, Gonzalez-Espinosa C, Garcia-Sainz JA. Norepinephrine- and phorbol ester-induced phosphorylation of ala-adrenergic receptors. Functional aspects. J Biol Chem 2000 275 6553-6559. 

Price RR, Morris DP, Biswas G, Smith MP, Schwinn DA. Acute agonist-mediated desensitization of the human ala-adrenergic receptor is primarily independent of carboxyl terminus regulation. Implications for regulation of ala AR splice variants. J Biol Chem 2002 277 9570-9579. 

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. 

StanasilaL, Perez JB, Vogel H, Cotecchia S. Oligomerization of the ala- and alb-adrenergic receptor subtypes. Potential implications in receptor internalization. J Biol Chem 2003 278 40,239 10,251. 

Day HEW, Campeau S, Watson SJ, Akil H. Distribution of ala, alb and ald adrenergic receptor mRNAs in the rat brain and spinal cord. J Chem Neuroanat 1997 13 115-139. 

Rokosh DG, Simpson PC. Knockout of the a, -adrenergic receptor subtype The ala/c is expressed in resistance arteries and is required to maintain arterial blood pressure. Proc Natl Acad Sci USA 2002 99 9474-9479. 

In this chapter we summarize some aspects of the structure-functional relationship of the ala and alb-adrenergic receptor subtypes related to the receptor activation process as well as the effect of different alpha-blockers on the constitutive activity of the receptor. Molecular modeling of the ala and alb-adrenergic receptor subtypes and computational simulation of receptor dynamics were useful to interpret the experimental findings derived from site directed mutagenesis studies. 2000 Elsevier Science B.V. All rights reserved. 

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