INT18577

Context Info Confidence 0.39 First Reported 1982 Last Reported 2005 Negated 0 Speculated 0 Reported most in Abstract Documents 20 Total Number 21 Disease Relevance 3.57 Pain Relevance 5.24

nucleus (Eef1a1) translation (Eef1a1) GTPase activity (Eef1a1) cytoplasm (Eef1a1)

Anatomy Link Frequency macrophages 1 plasma 1 myocytes 1 monocytes 1 muscle 1 Eef1a1 (Rattus norvegicus)

Pain Link Frequency Relevance Heat chemokine 4 100.00 agonist 16 99.98 noradrenaline 9 99.84 Potency 14 99.70 depression 2 98.54 Clonidine 23 98.36 medulla 1 97.12 antagonist 78 95.64 Catecholamine 5 92.72 Serotonin 1 92.40

Disease Link Frequency Relevance Heat Apoptosis 6 99.08 Repression 2 98.68 Depression 2 98.54 Cancer 7 97.96 Prostate Cancer 4 95.52 Cardiovascular Disease 2 93.12 INFLAMMATION 62 91.72 Heart Rate Under Development 4 88.68 Injury 8 87.04 Bordatella Infection 1 86.56

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

However, the depolarizing action of NE is attributable primarily to the alpha 1 adrenoceptor-mediated decrease in K+ conductance and not the beta adrenoceptor-dependent increase in lh.

Negative_regulation (decrease) of alpha 1

1) Confidence 0.39 Published 1996 Journal J. Neurosci. Section Abstract Doc Link 8551341 Disease Relevance 0 Pain Relevance 0.36

Conversely blockade of alpha 1 receptors up-regulated alpha 1 expression but not muscarinic receptor expression.

Negative_regulation (blockade) of alpha 1

2) Confidence 0.35 Published 1997 Journal Brain Res. Dev. Brain Res. Section Abstract Doc Link 9298232 Disease Relevance 0 Pain Relevance 0.33

Based on the potency ratio between alpha-1 and alpha-2 blocking activities, DHC or YO was most selective for alpha-1 or alpha-2 subtype, respectively, among the four YO analogs.

Negative_regulation (blocking) of alpha-1 associated with potency

3) Confidence 0.33 Published 1990 Journal Chem. Pharm. Bull. Section Abstract Doc Link 1976443 Disease Relevance 0 Pain Relevance 0.39

Structure-activity relationship of yohimbine and its related analogs in blocking alpha-1 and alpha-2 adrenoceptors: a comparative study of cardiovascular activities.

Negative_regulation (blocking) of alpha-1

4) Confidence 0.33 Published 1990 Journal Chem. Pharm. Bull. Section Title Doc Link 1976443 Disease Relevance 0 Pain Relevance 0.10

Phentolamine and SKF-7265, which block both alpha-1 and alpha-2 receptors, were also effective.

Negative_regulation (block) of alpha-1

5) Confidence 0.30 Published 1982 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 6124006 Disease Relevance 0.09 Pain Relevance 0.52

Blocking alpha 1-receptors revealed an alpha 2-like antiphosphaturic response.

Negative_regulation (Blocking) of alpha 1

6) Confidence 0.27 Published 1987 Journal Am. J. Physiol. Section Abstract Doc Link 3028153 Disease Relevance 0.08 Pain Relevance 0.08

To analyze and quantitate the alpha-2 adrenoceptor antagonism in the rat anococgygeus muscle, Schild analyses of clonidine-induced contractions against idazoxan were conducted either for idazoxan alone or after partially alkylating the alpha-1 adrenoceptors with phenoxybenzamine and by pharmacologic resultant analysis by blocking the alpha-1 adrenoceptors with prazosin.

Negative_regulation (blocking) of alpha-1 in muscle associated with clonidine

7) Confidence 0.21 Published 1989 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 2547934 Disease Relevance 0 Pain Relevance 0.24

We conclude that that antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of alpha 1- and alpha 2-adrenergic receptors.

Negative_regulation (blockade) of alpha 1

8) Confidence 0.19 Published 1984 Journal Circ. Res. Section Abstract Doc Link 6147208 Disease Relevance 0 Pain Relevance 0.17

Yohimbine reversed the inhibition. alpha 1 or beta-adrenoceptor agonists had little or no effect on glucose utilization.

Negative_regulation (inhibition.) of alpha 1 associated with agonist

9) Confidence 0.13 Published 1987 Journal FEBS Lett. Section Abstract Doc Link 2885223 Disease Relevance 0.09 Pain Relevance 0.44

Pretreatment with KGF at 72 h also attenuated the reduction of total lung capacity, decreased the alpha 1(I) procollagen mRNA levels, and diminished hydroxyproline accumulation due to HCl instillation.

Negative_regulation (decreased) of alpha 1 in lung

10) Confidence 0.10 Published 1996 Journal Am. J. Respir. Cell Mol. Biol. Section Abstract Doc Link 8879176 Disease Relevance 0.49 Pain Relevance 0.08

The increased concentration of norepinephrine leading to cardiac beta receptor stimulation combined with alpha-1 receptor inhibition may lead to increased apoptosis in myocytes.

Negative_regulation (inhibition) of alpha-1 in myocytes associated with apoptosis

11) Confidence 0.10 Published 2002 Journal Curr Control Trials Cardiovasc Med Section Body Doc Link PMC134479 Disease Relevance 0.65 Pain Relevance 0.18

Elevated plasma norepinephrine levels are hypothesized to cause direct myocardial damage through many mechanisms, which may be amplified by concomitant alpha-1 blockade.

Negative_regulation (blockade) of alpha-1 in plasma

12) Confidence 0.09 Published 2002 Journal Curr Control Trials Cardiovasc Med Section Body Doc Link PMC134479 Disease Relevance 0.69 Pain Relevance 0.15

The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin growth factor 1 (IGF1).

Negative_regulation (reduction) of factor 1

13) Confidence 0.07 Published 1995 Journal Cancer Chemother. Pharmacol. Section Abstract Doc Link 7540120 Disease Relevance 0.57 Pain Relevance 0.10

After 21 days of clorgyline treatment, the Bmax's of alpha-2-, alpha-1- and beta-adrenergic cortical receptors were reduced by 62, 36 and 34% respectively.

Negative_regulation (reduced) of alpha-1

14) Confidence 0.07 Published 1982 Journal Neuropharmacology Section Abstract Doc Link 6123960 Disease Relevance 0 Pain Relevance 0.28

Drugs which produce blockade of postjunctional alpha 1-adrenoceptors could also produce an increase in neurogenic release of noradrenaline due to blockade of prejunctional alpha 1-adrenoceptors, and this might result in more complex effects than would be anticipated.

Negative_regulation (blockade) of alpha 1 associated with noradrenaline

15) Confidence 0.07 Published 1986 Journal J. Mol. Cell. Cardiol. Section Abstract Doc Link 2433457 Disease Relevance 0 Pain Relevance 0.32

Drugs which produce blockade of postjunctional alpha 1-adrenoceptors could also produce an increase in neurogenic release of noradrenaline due to blockade of prejunctional alpha 1-adrenoceptors, and this might result in more complex effects than would be anticipated.

Negative_regulation (blockade) of alpha 1 associated with noradrenaline

16) Confidence 0.07 Published 1986 Journal J. Mol. Cell. Cardiol. Section Abstract Doc Link 2433457 Disease Relevance 0 Pain Relevance 0.34

The overall depression of the cAMP response to NE in progesterone-exposed slices may involve a decrease of alpha 1 receptor facilitation of cAMP synthesis.

Negative_regulation (decrease) of alpha 1 associated with depression

17) Confidence 0.04 Published 1989 Journal Brain Res. Mol. Brain Res. Section Abstract Doc Link 2541302 Disease Relevance 0.17 Pain Relevance 0.47

These findings suggest that alpha adrenoceptor agonists inhibit renin release from rat kidney cortical slices mainly via alpha-1 adrenoceptors and that calcium influx followed by the activation of the calcium-calmodulin system is involved in the above inhibition.

Negative_regulation (inhibit) of alpha-1 in kidney associated with agonist

18) Confidence 0.04 Published 1985 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 2989497 Disease Relevance 0 Pain Relevance 0.23

Systemic administration of 3-nitro-L-tyrosine markedly inhibits the subsequent hemodynamic responses to alpha 1- and beta-adrenoceptor agonists in anesthetized rats.

Negative_regulation (inhibits) of alpha 1 associated with agonist

19) Confidence 0.04 Published 1996 Journal Eur. J. Pharmacol. Section Abstract Doc Link 8960880 Disease Relevance 0 Pain Relevance 0.09

An attractive hypothesis for WAY-169916-mediated activity in the spleen involves the downregulation of LBP and CD14 expression on monocytes and macrophages, resulting in a diminished immune response and ultimately resulting in the observed decreases in MMP9, IL1R2, chemokine-like factor 1, S100A8, and S100A9 through the repression of NF-?

Negative_regulation (decreases) of factor 1 in monocytes associated with chemokine and repression

20) Confidence 0.01 Published 2005 Journal Arthritis Res Ther Section Body Doc Link PMC1174937 Disease Relevance 0.37 Pain Relevance 0.19

General Comments

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