Molecular mechanisms of beta2-adrenergic receptor function and regulation.

@article{citeulike:512287, abstract = {It is now clear that the beta2-adrenergic receptor continuously oscillates between various conformations in the basal state, and that agonists act to stabilize one or more conformations. It is conceivable that synthetic agonists might be engineered to preferentially confine the receptor to certain conformations deemed clinically important while having a less stabilizing effect on unwanted conformations. In addition, studies of genetically engineered mice have revealed previously unrecognized cross-talk between the beta2-receptor and phospholipase C, such that removal of the primary dilating pathway results in downregulation of constrictive pathways and overactivity of the dilating pathway increases the contractile response. These results indicate a dynamic interaction between beta2-receptor activity and Gq-coupled receptors that constrict the airway. Potentially, then, during chronic beta-agonist therapy, expression of phospholipase C is increased, the functions of Gq-coupled constrictive receptors are enhanced, and there may be an increased tendency for clinical decompensation due to asthma and chronic obstructive pulmonary disease triggers. Antagonists to these receptors might be able to act synergistically with chronic beta-agonists to block the effect of phospholipase C. Alternatively, perhaps novel phospholipase C antagonists would provide the most efficacious approach to blocking the physiologic sequelae of cross-talk between the beta2-receptor and phospholipase C.}, address = {CardioPulmonary Research Center, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0564, Cincinnati, OH 45267-0564, USA.}, author = {McGraw, D. W. and Liggett, S. B. }, citeulike-article-id = {512287}, doi = {10.1513/pats.200504-027SR}, issn = {1546-3222}, journal = {Proc Am Thorac Soc}, keywords = {activation, agonist, b2ar}, number = {4}, posted-at = {2006-02-20 09:27:39}, priority = {3}, title = {Molecular mechanisms of beta2-adrenergic receptor function and regulation.}, url = {http://dx.doi.org/10.1513/pats.200504-027SR}, volume = {2}, year = {2005} }

TY - JOUR ID - citeulike:512287 L3 - citeulike-article-id:512287 TI - Molecular mechanisms of beta2-adrenergic receptor function and regulation. JF - Proc Am Thorac Soc VL - 2 IS - 4 AD - CardioPulmonary Research Center, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0564, Cincinnati, OH 45267-0564, USA. SN - 1546-3222 N2 - It is now clear that the beta2-adrenergic receptor continuously oscillates between various conformations in the basal state, and that agonists act to stabilize one or more conformations. It is conceivable that synthetic agonists might be engineered to preferentially confine the receptor to certain conformations deemed clinically important while having a less stabilizing effect on unwanted conformations. In addition, studies of genetically engineered mice have revealed previously unrecognized cross-talk between the beta2-receptor and phospholipase C, such that removal of the primary dilating pathway results in downregulation of constrictive pathways and overactivity of the dilating pathway increases the contractile response. These results indicate a dynamic interaction between beta2-receptor activity and Gq-coupled receptors that constrict the airway. Potentially, then, during chronic beta-agonist therapy, expression of phospholipase C is increased, the functions of Gq-coupled constrictive receptors are enhanced, and there may be an increased tendency for clinical decompensation due to asthma and chronic obstructive pulmonary disease triggers. Antagonists to these receptors might be able to act synergistically with chronic beta-agonists to block the effect of phospholipase C. Alternatively, perhaps novel phospholipase C antagonists would provide the most efficacious approach to blocking the physiologic sequelae of cross-talk between the beta2-receptor and phospholipase C. KW - activation KW - agonist KW - b2ar AU - McGraw, DW AU - Liggett, SB PY - 2005/// UR - http://dx.doi.org/10.1513/pats.200504-027SR ER -