Disease relevance of Adra1b

• Overexpression of the alpha1B-adrenergic receptor causes apoptotic neurodegeneration: multiple system atrophy [1].
• Hypotension, autonomic failure, and cardiac hypertrophy in transgenic mice overexpressing the alpha 1B-adrenergic receptor [2].
• OBJECTIVES: Using a transgenic mouse model of myocardial-targeted overexpression of the wild-type alpha1B adrenergic receptor (AR) (Tg alpha43), we studied the role of the betaAR kinase (betaARK1) in the evolution of myocardial hypertrophy and its transition to heart failure (HF) [3].
• Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity [4].
• Dominance of the alpha1B-adrenergic receptor and its subcellular localization in human and TRAMP prostate cancer cell lines [5].

High impact information on Adra1b

• We studied cardiac pressure overload in mice with double KO of the 2 main alpha1-AR subtypes in the heart, alpha 1A (Adra1a) and alpha 1B (Adra1b) [6].
• Decreased blood pressure response in mice deficient of the alpha1b-adrenergic receptor [7].
• Transgenic mice were generated by using the alpha-myosin heavy chain promoter coupled to the coding sequence of a constitutively active mutant alpha 1B-adrenergic receptor (AR) [8].
• Myocardial expression of a constitutively active alpha 1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy [8].
• To assess the role of the alpha1b-adrenergic receptor (AR) in glucose homeostasis, we investigated glucose metabolism in knockout mice deficient of this receptor subtype (alpha1b-AR-/-) [9].

Biological context of Adra1b

• Impaired glucose homeostasis in mice lacking the alpha1b-adrenergic receptor subtype [9].
• We have now cloned two alpha 1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster alpha 1B-adrenergic receptor as a probe [10].
• Gene expression profile of neurodegeneration induced by alpha1B-adrenergic receptor overactivity: NMDA/GABAA dysregulation and apoptosis [11].
• Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells [12].
• Experimental and computational mutagenesis of the alpha1b-adrenergic receptor have been instrumental in elucidating some of the molecular mechanisms underlying receptor activation and receptor coupling to Gq [13].

Anatomical context of Adra1b

• Critical role for the alpha-1B adrenergic receptor at the sympathetic neuroeffector junction [14].
• Mouse alpha1B-adrenergic receptor is expressed in neurons and NG2 oligodendrocytes [15].
• However, morphine-induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the alpha1b-adrenergic receptor (alpha1b-AR KO) and in wild-type (WT) mice, suggesting the presence of a compensatory mechanism [16].

Associations of Adra1b with chemical compounds

• Treatment with chloroethylclonidine (10 microM, for 30 min at 37 degrees, with subsequent washout) abolished [3H]prazosin binding to alpha 1B-adrenoceptors in rat spleen almost completely and reduced specific binding in rat kidney and cerebral cortex by a percentage comparable to the known alpha 1B-adrenoceptor content of these tissues [17].
• SR46349B also completely blocked, in alpha1b-AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and D-amphetamine (2 mg/kg) [16].
• We have previously demonstrated that overexpression of alpha1B-adrenergic receptor (alpha1BAR) in transgenic mice leads to a marked desensitization of betaAR-mediated adenylyl cyclase stimulation which is correlated with increased levels of activated protein kinase C (PKC) beta, delta and [J. Mol. Cell. Cardiol. 30 (1998) 1827] [18].
• The role of alpha1b-ARs in this effect was then verified in alpha1b-AR KO mice: whereas dexefaroxan (1 mg/kg) doubled locomotor hyperactivity induced by GBR 12783 (14 mg/kg) in WT mice, it decreased it by 43% in alpha1b-AR KO mice [19].
• Recent experiments have shown that mice lacking the alpha1b-adrenergic receptor (alpha1b-AR KO) are less responsive to the locomotor hyperactivity induced by psychostimulants, such as D-amphetamine or cocaine, than their wild-type littermates (WT) [19].

Enzymatic interactions of Adra1b

• One of the mechanisms involved in the modulation of receptor function is the phosphorylation of specific residues by intracellular kinases. alpha1b-Adrenergic receptor is phosphorylated in vitro by cAMP-dependent protein kinase (PKA), although its physiological effect remains to be determined [20].

Regulatory relationships of Adra1b

• Overexpression of alpha1B-adrenergic receptor induces left ventricular dysfunction in the absence of hypertrophy [21].

Other interactions of Adra1b

• Transgenic mice were generated with cardiac-specific overexpression of the wild-type (WT) alpha1B-adrenergic receptor (AR) using the murine alpha-myosin heavy chain gene promoter [22].
• Systemic overexpression of the alpha 1B-adrenergic receptor in mice: an animal model of epilepsy [23].
• Phosphorylation of the third intracellular loop of the mouse alpha1b-adrenergic receptor by cAMP-dependent protein kinase [20].

Analytical, diagnostic and therapeutic context of Adra1b

• A partial cDNA encoding most of the third intracellular loop of the chicken alpha 1b adrenergic receptor subtype, obtained by reverse transcription-polymerase chain reaction (RT-PCR) techniques using degenerate primers derived from mammalian sequences, was used to isolate an alpha 1b adrenergic receptor cDNA from brain [24].

References