INT7717

Context Info Confidence 0.70 First Reported 1983 Last Reported 2009 Negated 2 Speculated 3 Reported most in Abstract Documents 62 Total Number 65 Disease Relevance 17.68 Pain Relevance 27.32

signal transduction (Adra2a) plasma membrane (Adra2a) cytoplasm (Adra2a) signal transducer activity (Adra2a)

Anatomy Link Frequency spinal 5 brain 3 nucleus 3 central nervous system 3 nerve 3 Adra2a (Mus musculus)

Pain Link Frequency Relevance Heat agonist 97 100.00 Opioid 35 100.00 analgesia 18 100.00 opioid receptor 15 100.00 Neuropathic pain 6 100.00 medulla 5 100.00 transcutaneous nerve stimulation 9 99.98 Spinal cord 9 99.96 Inflammation 5 99.90 Clonidine 93 99.84

Disease Link Frequency Relevance Heat Nervous System Injury 8 100.00 Neuropathic Pain 6 100.00 Neuroblastoma 1 100.00 INFLAMMATION 5 99.90 Hypertension 27 99.84 Bordatella Infection 14 99.84 Targeted Disruption 11 99.82 Diabetes Mellitus 34 99.76 Suicidal Behaviour 24 99.70 Hypotension 4 99.46

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

These two drugs seem to require the alpha2A AR for spinal analgesia when given separately; when delivered as a combination, the resultant synergistic interaction requires the alpha2C AR as well.

Positive_regulation (requires) of alpha2C AR in spinal

1) Confidence 0.70 Published 2009 Journal Anesthesiology Section Body Doc Link 19212267 Disease Relevance 0 Pain Relevance 0

The results suggest that alpha2-AR agonist-induced ventilatory excitation (tachypnea) requires the activation of alpha2A-ARs whereas clonidine-induced ventilatory depression (arrhythmic breathing) requires the activation of an alternate alpha2-AR subtype (presumably alpha2C-ARs).

Positive_regulation (activation) of alpha2-AR associated with depression, respiratory failure, agonist and clonidine

2) Confidence 0.68 Published 2001 Journal Respir Physiol Section Abstract Doc Link 11282385 Disease Relevance 0.19 Pain Relevance 0.62

These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of alpha2A-adrenoceptors.

Positive_regulation (activation) of alpha2A associated with pain threshold and endep

3) Confidence 0.67 Published 2000 Journal Jpn. J. Pharmacol. Section Abstract Doc Link 10877531 Disease Relevance 0.19 Pain Relevance 0.94

By means of quantitative real-time PCR we show that mRNAs encoding the alpha(2A)-adrenergic receptor (alpha(2A)AR) and the alpha(2C)-adrenergic receptor (alpha(2C)AR) are up-regulated in the brainstem, and that alpha(2C)AR mRNA is also elevated in the hippocampus and striatum of NET-KO mice.

Positive_regulation (up-regulated) of alpha(2A)AR in striatum associated with medulla and hippocampus

4) Confidence 0.67 Published 2006 Journal J. Neurochem. Section Abstract Doc Link 16417582 Disease Relevance 0.07 Pain Relevance 0.47

The endogenous catecholamines adrenaline and noradrenaline mediate their biological actions via activation of nine different adrenergic receptor subtypes, three alpha 1-receptors (alpha 1A, alpha 1B, alpha 1D), three alpha 2-receptors (alpha 2A, alpha 2B, alpha 2C) and three beta-receptors (beta 1, beta 2, beta 3).

Positive_regulation (activation) of alpha 2A associated with catecholamine and noradrenaline

5) Confidence 0.67 Published 2001 Journal Z Kardiol Section Abstract Doc Link 11677796 Disease Relevance 0.14 Pain Relevance 0.18

Transcutaneous electrical nerve stimulation activates peripherally located alpha-2A adrenergic receptors.

Positive_regulation (activates) of alpha-2A in nerve associated with transcutaneous nerve stimulation

6) Confidence 0.67 Published 2005 Journal Pain Section Title Doc Link 15911163 Disease Relevance 0.06 Pain Relevance 1.18

We speculate that future development of agents capable of selectively activating the alpha2A-AR or blocking the alpha2B-AR may further improve our capability to treat hypertension, ischemic heart disease and heart failure.

Positive_regulation (activating) of alpha2A-AR in heart associated with coronary artery disease, hypertension and myocardial infarction

7) Confidence 0.66 Published 2001 Journal J. Hypertens. Section Abstract Doc Link 11725152 Disease Relevance 1.27 Pain Relevance 0.30

The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha2A-AR subtype, which is the predominant alpha2-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha2B-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha2B-AR).

Positive_regulation (requires) of alpha2B-AR in central nervous system associated with hypertension, hypotension and central nervous system

8) Confidence 0.66 Published 2001 Journal J. Hypertens. Section Abstract Doc Link 11725152 Disease Relevance 0.94 Pain Relevance 0.34

These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine.

Positive_regulation (stimulation) of alpha 2-adrenoceptor in head

9) Confidence 0.61 Published 1997 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 9164589 Disease Relevance 0 Pain Relevance 0.07

These two drugs seem to require the alpha2A AR for spinal analgesia when given separately; when delivered as a combination, the resultant synergistic interaction requires the alpha2C AR as well.

Spec (seem) Positive_regulation (require) of alpha2A AR in spinal

10) Confidence 0.61 Published 2009 Journal Anesthesiology Section Body Doc Link 19212267 Disease Relevance 0 Pain Relevance 0

The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain alpha2A-adrenoceptors.

Positive_regulation (increase) of alpha2A-adrenoceptors in brain associated with depression

11) Confidence 0.60 Published 1998 Journal J. Neurochem. Section Abstract Doc Link 9489732 Disease Relevance 0.74 Pain Relevance 0.47

These results indicate that clonidine and guanabenz impaired memory processes in a mouse passive avoidance paradigm through the selective activation of the alpha2A-adrenoceptor subtype.

Positive_regulation (activation) of alpha2A-adrenoceptor associated with clonidine

12) Confidence 0.51 Published 2004 Journal Behav. Brain Res. Section Abstract Doc Link 15265636 Disease Relevance 0.29 Pain Relevance 0.61

The studies employed two genetically engineered mouse strains, having either a targeted inactivation of the alpha2C-AR gene (alpha2C-KO) or over-expressing the alpha2C-AR (alpha2C-OE).

Positive_regulation (inactivation) of alpha2C-AR associated with sprains and strains

13) Confidence 0.50 Published 2001 Journal Life Sci. Section Abstract Doc Link 11358337 Disease Relevance 0.44 Pain Relevance 0.18

The studies employed two genetically engineered mouse strains, having either a targeted inactivation of the alpha2C-AR gene (alpha2C-KO) or over-expressing the alpha2C-AR (alpha2C-OE).

Positive_regulation (inactivation) of alpha2C-AR associated with sprains and strains

14) Confidence 0.50 Published 2001 Journal Life Sci. Section Abstract Doc Link 11358337 Disease Relevance 0.43 Pain Relevance 0.17

Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims.

Positive_regulation (increase) of alpha2A in brains associated with suicidal behaviour and agonist

15) Confidence 0.49 Published 1998 Journal J. Neurochem. Section Title Doc Link 9489732 Disease Relevance 0.81 Pain Relevance 0.31

The analgesic efficacy of partial opioid agonists is increased in mice with targeted inactivation of the alpha2A-adrenoceptor gene.

Positive_regulation (inactivation) of alpha2A associated with pain, mu agonist and analgesic

16) Confidence 0.49 Published 2006 Journal Eur. J. Pharmacol. Section Title Doc Link 16325800 Disease Relevance 0 Pain Relevance 1.40

Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors.

Positive_regulation (up-regulation) of alpha2A in brain associated with targeted disruption

17) Confidence 0.49 Published 2006 Journal J. Neurochem. Section Title Doc Link 16417582 Disease Relevance 0.10 Pain Relevance 0.32

The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha2A-AR subtype, which is the predominant alpha2-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha2B-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha2B-AR).

Positive_regulation (activation) of alpha2A-AR in central nervous system associated with hypertension, hypotension and central nervous system

18) Confidence 0.48 Published 2001 Journal J. Hypertens. Section Abstract Doc Link 11725152 Disease Relevance 0.58 Pain Relevance 0.31

The effects of prazosin and yohimbine on the vasopressor response to sympathetic nerve stimulation, and to i.v. administration of norepinephrine were studied in the pithed rat to ascertain whether prazosin and yohimbine would preferentially block pressure responses due to exogenous versus endogenous alpha-adrenergic receptor activation.

Spec (whether) Positive_regulation (activation) of alpha-adrenergic receptor in nerve

19) Confidence 0.45 Published 1984 Journal Res. Commun. Chem. Pathol. Pharmacol. Section Abstract Doc Link 6322258 Disease Relevance 0 Pain Relevance 0

The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha2A-AR subtype, which is the predominant alpha2-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha2B-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha2B-AR).

Positive_regulation (activation) of alpha2B-AR in central nervous system associated with hypertension, hypotension and central nervous system

20) Confidence 0.44 Published 2001 Journal J. Hypertens. Section Abstract Doc Link 11725152 Disease Relevance 0.89 Pain Relevance 0.33

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