Disease relevance of ADRA2C

• Sequence variations in the human alpha2 adrenergic receptor genes (ADRA2A and ADRA2C) have been implicated as a cause of hypertension in blacks [1].
• The alpha 2-adrenoceptors of the human retinoblastoma cell line (Y79) may represent an additional example of the alpha 2C-adrenoceptor [2].

High impact information on ADRA2C

• The closely related alpha 2CAR subtype denoted alpha 2C4 lacks a cysteine in this region and has different G-protein-coupling characteristics and agonist regulatory properties as compared to alpha 2C10 [3].
• Cell-type specific targeting of the alpha 2c-adrenoceptor. Evidence for the organization of receptor microdomains during neuronal differentiation of PC12 cells [4].
• Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. II. Preferential coupling of the alpha 2C-adrenergic receptor to the guanine nucleotide-binding protein, Go [5].
• In this study we tested the genes for two adrenergic receptors, alpha 1C (ADRA1C) located on chromosome 8p11.2, and alpha 2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in ADHD [6].
• The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia [7].

Biological context of ADRA2C

• ADRA2C had one haplotype block of 10 kb in Caucasians only [8].
• The gene encoding the brain alpha 2-adrenergic receptor (ADRA2C) is located on human chromosome 4 [9].
• Both the DraI restriction fragment length polymorphism in ADRA2A and the ADRA2C (Del 322 to 325) can be excluded as major candidate alleles for hypertension in blacks [1].
• We tested the hypotheses that clinical response and cognitive improvement to antipsychotic treatment are associated with genetic variation in adrenergic alpha2C receptor (ADRA2C) [10].
• Heterologous expression of the cloned guinea pig alpha 2A, alpha 2B, and alpha 2C adrenoceptor subtypes. Radioligand binding and functional coupling to a CAMP-responsive reporter gene [11].

Anatomical context of ADRA2C

• Additionally, Purkinje cells of the anterior lobe vermis (lobules I to V) and uvula/tonsil (lobules IX/HIX) express alpha 1a and alpha 2c subtypes, and Purkinje cells in the ansiform lobule (lobule HVII) and uvula/tonsil express alpha 1b and alpha 2c adrenergic receptor subtypes [12].
• Previously unreported heterogeneity in alpha 2AR subtype distribution (alpha 2a and alpha 2bAR mRNA present, alpha 2cAR mRNA virtually absent) is found at all sites of alpha 2AR mRNA expression in human spinal cord, including locations known to mediate effects of alpha 2AR agonist drugs on nociception, autonomic function and motor tone [13].
• Cloning and expression of the alpha 2C-adrenergic receptor from the OK cell line [14].
• Distribution of alpha 2A- and alpha 2C-adrenergic receptor immunoreactivity in the central nervous system [15].

Associations of ADRA2C with chemical compounds

• In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases [7].
• Norepinephrine displayed, respectively, 18- and 31-fold selectivity for the high affinity state of the alpha-2C adrenoceptor as compared to alpha-2A- or alpha-2B adrenoceptors, and was > 100,000- fold selective over platelet I1-imidazoline sites [16].
• A linkage study with D5 dopamine and alpha 2C-adrenergic receptor genes in six multiplex bipolar pedigrees [17].
• The two lacZ deletions, delta N 11-75 and delta C 82-1023, were first characterized by fusing to two small interacting peptides and were then further analyzed by fusing to three membrane receptors (G protein-coupled receptors alpha 2cAR and D2DRL and receptor tyrosine kinase insulin receptor) that were known to form homodimers in the membrane [18].
• Down-regulation of the alpha-2C adrenergic receptor: involvement of a serine/threonine motif in the third cytoplasmic loop [19].

Other interactions of ADRA2C

• Three genes encode alpha2-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325) [8].
• These findings exclude a strong effect of this ADRA2C marker on risk for ADHD in our sample of adult proband families [20].
• The investigation of families carrying recombinant chromosomes, pulsed-field analysis, and genomic walking mapped the ADRA2C gene adjacent to D4S81, 500 kb proximal to the HD gene [9].

Analytical, diagnostic and therapeutic context of ADRA2C

• Subtype-specific probes to the murine homologs of the human ADRA2B and ADRA2C genes were prepared by PCR amplification and used to map these two genes to mouse chromosomes 2 and 5, respectively [21].
• In a logistic model that controlled for age, body mass index, diabetes, and smoking, the adjusted odds ratio (OR) for hypertension was 1.0 (95% CI, 0.8 to 1.2), and 1.0 (95% CI, 0.9 to 1.2) for ADRA2A and ADRA2C variant alleles [1].
• Through molecular cloning, the existence of three distinct subtypes of alpha 2-adrenergic receptors (alpha 2AR)--A, B and C--has been established and are referred to as alpha 2A AR, alpha 2B AR and alpha 2CAR [22].
• Effects of a alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression [23].

References