ADRA2A

ADRA2A

A gene on chromosome 10q24-q26 that encodes alpha-2A-adrenergic receptor, a member of the G protein-coupled receptor superfamily, which plays a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the CNS, smooth muscle contraction and thermoregulation.
 
ADRA2A agonists
Oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine.
 
ADRA2A antagonists
Yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
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However there are evidences that polymorphisms of the ADRA2B and the ADRA2A genes could be involved (Bea et al., 2010; Phares et al., 2004).
On the other hand, 22 SNPs were exclusively related to a specific lipid--4 for TC: rs569805 (ABCB11), rs494874 (ABCB11), rs1801260 (CLOCK), andrs6013029 (CTNNBL1); 3 for LDL-c: rs7799039 (LEP), rs7498665 (SH2B1), and rs7359397 (SH2B1); 9 for HDL-c: rs2815752 (NEGR1), rs-2943641 (IRS1), rs2419621 (ACSL5), rs6265 (BDNF), rs110-30104 (BDNF), rs4769873 (ALOX5AP), rs9939609 (FTO), rs6567160 (MC4R), and rs2287019 (QPCTL); and 6 for TG: rs324420 (FAAH), rs2959272 (PPARG), rs1386835 (PPARG), rs709158 (PPARG), rs1175540 (PPARG), rs1800544 (ADRA2A) (Figure 1).
The gene expression of four adrenoceptors, alpha 1(ADRA1A), alpha 2 (ADRA2A), beta 1 (ADRB1), and beta 2 (ADRB2), as well as of three muscarinic receptors, M2 (CHRM2), M3 (CHRM3), and M4 (CHRM4), was detected with high expression of beta 2 (ADRB2) and M3 (CHRM3) (Figure 3).
In humans, a polymorphism of [alpha](2A)AR gene (ADRA2A) was reportedly associated with an increased risk for type 2 DM [46].
ADRA2A is a protein belonging to the GPCR family and is involved in the regulation of neurotransmitter release from adrenergic neurons in the CNS [90].
The [AC.sub.50] values for amitraz for [alpha]-2A and [alpha]-2b adrenergic receptors were 0.05-1.6 [micro]M (ADRA2A, Adra2a, Adra2b), but this was not the case for other adrenergic receptor subtypes [[alpha]-2C (ADRA2C), [beta]-1 (ADRBI), [beta]-2 (ADRB2), P-3 (ADRB3)].
Called yohimbine, the drug is effective in people with a variant of a gene called ADRA2A, researchers report October 8 in Science Translational Medicine.
[39] Among NE system genes, researchers have primarily focused on the noradrenaline transporter (NET1/SLC6A2) and on the adrenergic alpha receptors 2A and 2C (ADRA2A and ADRA2C).
Thus, polymorphisms in the ADRA2A gene, which encodes adrenergic receptors that inhibit norepinephrine release from the neuron, are associated with certain aspects of the stress response as determined by measuring blood pressure and heart rate (Finley et al.
An initial 25 lead SNPs were followed up in 76 558 additional study participants, and 9 new loci were found to be associated (P < 5 x [10.sup.-8]) with fasting glucose (and/or HOMA-B) [adenylate cyclase 5 (ADCY5); MAP-kinase activating death domain (MADD); cryptochrome 2 (photolyase-like) (CRY2); adrenergic, alpha-2A-, receptor (ADRA2A); fatty acid desaturase 1 (FADS1); prospero homeobox 1 (PROX1); solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2); GLIS family zinc finger 3 (GLIS3); and C2 calcium-dependent domain containing 4B (C2CD4B)] and 1 was found to be associated with fasting insulin and HOMA-IR concentrations [insulin-like growth factor 1 (somatomedin C) (IGF1)].