In vitro and ex vivo effects of β2-adrenoceptor variations
| Variation | Parameter | Cell/Tissue | Variant Effect | Reference |
|---|---|---|---|---|
| c.-47T>C | Overexpression in cell lines | |||
| ADRB2 density | COS-7 | T > C (“Cys > Arg”) | McGraw et al. (1998) | |
| Endogenous receptor | ||||
| ADRB2 density | HASM | T > C (“Cys > Arg”) | McGraw et al. (1998) | |
| Lymphocytes | T = C (“Cys = Arg”) | Lipworth et al. (2002) | ||
| c.46G>A (p.Gly16Arg) | Overexpression in cell lines | |||
| Agonist binding affinity | CHW-1102 | Gly = Arg | Green et al. (1994) | |
| HEK-293 | Gly = Arg | Ahles et al. (2011) | ||
| Speed of ADRB2 activation | HEK-293 | Gly > Arg | Ahles et al. (2011) | |
| Basal/maximal isoproterenol-stimulated AC activity (membranes) | CHW-1102 | Gly = Arg | Green et al. (1994) | |
| EPI-stimulated cAMP formation | HEK-293 | Gly > Arg | Ahles et al. (2011) | |
| Endogenous receptor | ||||
| ADRB2 density | Lymphocytes | Gly = Arg | Lipworth et al. (1999) | |
| Basal/maximal isoproterenol-stimulated AC activity | Lymphocytes | Gly = Arg | Lipworth et al. (1999) | |
| Lymphocytes | Gly = Arg | Bruck et al. (2003a) | ||
| HASM | Gly = Arg | Moore et al. (2000) | ||
| Agonist-induced downregulation | Lymphocytes | Gly > Arg | Lipworth et al. (1999) | |
| HLM | Gly < Arg | Chong et al. (2000) | ||
| Lymphocytes | Gly > Arg | Aziz et al. (1998) | ||
| Terbutaline-induced lipolysis | Adipocytes | Gly > Arg | Large et al. (1997) | |
| Basal/maximal lipolysis | Adipocytes | Gly = Arg | Large et al. (1997) | |
| EPI-induced inotropic and lusitropic effect | Right atria (48 failing + β-blocker) | Gly = Arg | Molenaar et al. (2007) | |
| c.79G>C (p.Gln27Glu) | Overexpression in cell lines | |||
| Agonist binding affinity | CHW-1102 | Gln = Glu | Green et al. (1994) | |
| Basal/maximal isoproterenol-stimulated AC activity (membranes) | CHW-1102 | Gln = Glu | Green et al. (1994) | |
| Endogenous receptor | ||||
| ADRB2 density | Lymphocytes | Gln = Glu | Lipworth et al. (1999) | |
| Basal/maximal isoproterenol-stimulated AC activity | Lymphocytes | Gln = Glu | Lipworth et al. (1999) | |
| Lymphocytes | Gln = Glu | Bruck et al. (2003a) | ||
| Agonist-induced downregulation | HLM | Gln > Glu | Chong et al. (2000) | |
| Short- and long-term desensitization | HASM | Gln > Glu | Moore et al. (2000) | |
| EPI-induced inotropic and lusitropic effect | Right atria (48 failing + β-blocker) | Gln = Glu | Molenaar et al. (2007) | |
| c.[46G>A;79G>C] (p.[Gly16Arg;Gln27Glu]) | Isoproterenol -induced relaxation of internal mammary arteries | Arterial segments | ArgGln = GlyGlu > GlyGln | Khalaila et al. (2007) |
| c.491C>T (p.Thr164Ile) | Overexpression in cell lines | |||
| Agonist binding affinity | CHW-1102 | Thr > Ile | Green et al. (1993) | |
| Basal/maximal isoproterenol-stimulated AC activity (membrane preparations) | CHW-1102 | Thr > Ile | Green et al. (1993) | |
| Endogenous receptor | ||||
| Isoproterenol -stimulated cAMP formation | Lymphocytes | Thr > Ile | Büscher et al. (2002) | |
| Agonist-induced downregulation | Lymphocytes | Thr > Ile | Lipworth et al. (1999) | |
| Terbutaline-induced lipolysis | Adipocytes | Thr > Ile | Hoffstedt et al. (2001) | |
| Isoproterenol-induced inhibition of IgE-mediated histamine release | HLM | Thr > Ile | Kay et al. (2007) | |
| Salmeterol/terbutaline-induced inhibition of IgE-mediated histamine release | HLM | Thr > Ile | Kay et al. (2003) | |
| Basal/maximal histamine release | Thr = Ile |
Receptor expression in overexpression systems: > 0.5 pmol/mg membrane protein. EPI, epinephrine; HASM, human airway smooth muscle; HLM, human lung mast cell.