INT118107

Context Info Confidence 0.66 First Reported 2004 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 4 Total Number 14 Disease Relevance 6.89 Pain Relevance 2.99

signal transduction (Avpr1b) plasma membrane (Avpr1b) response to stress (Avpr1b) signal transducer activity (Avpr1b)

Anatomy Link Frequency PVN 2 pyramidal neurons 1 anterior 1 pancreas 1 adrenal medulla 1 Avpr1b (Mus musculus)

Pain Link Frequency Relevance Heat fluoxetine 10 99.78 Pyramidal cell 11 99.52 antagonist 187 99.20 medulla 66 99.20 agonist 99 98.88 Catecholamine 33 98.60 antidepressant 17 98.36 Hippocampus 44 97.88 amygdala 11 94.40 Morphine 11 93.88

Disease Link Frequency Relevance Heat Stress 885 99.98 Targeted Disruption 670 99.96 Sprains And Strains 132 99.70 Affective Disorder 25 99.24 Pain 1 93.56 Depression 115 81.20 Aggression 187 79.12 Diabetes Mellitus 11 77.20 Obesity 33 76.48 Hypersensitivity 33 65.92

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

fragment is threefold greater than that of the C57BL/6 strain confirming an increase in Avpr1b promoter activity with the “long” form of microsatellite (see, Figure 1B and C), in a reporter assay in COS-7 cells.

Positive_regulation (increase) of Avpr1b associated with sprains and strains

1) Confidence 0.66 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.56 Pain Relevance 0.03

Stimulation of the Avpr1b in the rat adrenal medulla causes catecholamine secretion (Grazzini et al. 1998).

Positive_regulation (Stimulation) of Avpr1b in adrenal medulla associated with medulla and catecholamine

2) Confidence 0.66 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.34 Pain Relevance 0.26

The preferential expression of Avp in the pPVN in adaptation to chronic stress observed in rats is associated with an upregulation of Avpr1bs (but not Crh receptors) in the anterior pituitary gland (Aguilera 1994).

Positive_regulation (upregulation) of Avpr1bs in gland associated with stress

3) Confidence 0.66 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.80 Pain Relevance 0.09

Comparisons of Oxtr mRNA levels in Avpr1b KO and wild-type mouse anterior pituitaries appear to suggest an upregulation of Oxtrs in Avpr1b KO mice (Nakamura et al. 2008).

Positive_regulation (upregulation) of Avpr1b in anterior associated with targeted disruption

4) Confidence 0.57 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.88 Pain Relevance 0.03

Our studies in Avpr1b KO mice (Lolait et al. 2007a,b; Stewart et al. 2008a,b) and similar studies on acute stress in Brattleboro rats (Domokos et al. 2008; Zelena et al. 2009) both often note a disparity between stress-induced ACTH versus CORT release in Avp/Avpr1b-deficient animals.

Positive_regulation (induced) of Avpr1b associated with stress and targeted disruption

5) Confidence 0.47 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.93 Pain Relevance 0

We cannot totally rule out the possibility that mechanisms compensating for the loss of Avpr1b are active in the Avpr1b KO.

Positive_regulation (active) of Avpr1b associated with targeted disruption

6) Confidence 0.47 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.60 Pain Relevance 0

One laboratory that used agonists and antagonists to Avp/Oxt receptors (but notably none selective for Avpr1bs) in ?

Neg (none) Positive_regulation (selective) of Avpr1bs associated with antagonist and agonist

7) Confidence 0.47 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.13 Pain Relevance 0.14

-cell lines (Yibchok-anun and Hsu 1998) and perfused rat pancreas (Yibchok-anun et al. 1999) produced contrasting results, the latter study suggesting glucagon secretion in response to Avp, and Oxt is mediated through the activation of Avpr1bs and Oxtrs, respectively, rather than any activity of Avp on Oxtrs.

Positive_regulation (activation) of Avpr1bs in pancreas

8) Confidence 0.47 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.22 Pain Relevance 0.12

The data suggests that the Avpr1b is required to drive the HPA axis response to acute antidepressant treatment and provides further evidence of a sexual dichotomy in the regulation of PVN Avp/Oxt gene expression following antidepressant administration.

Positive_regulation (required) of Avpr1b in PVN associated with antidepressant

9) Confidence 0.47 Published 2008 Journal Psychoneuroendocrinology Section Abstract Doc Link 18243568 Disease Relevance 0.53 Pain Relevance 0.89

In contrast, fluoxetine treatment increased PVN Avp mRNA levels in female Avpr1b wild type but not KO animals.

Positive_regulation (increased) of Avpr1b in PVN associated with targeted disruption and fluoxetine

10) Confidence 0.47 Published 2008 Journal Psychoneuroendocrinology Section Abstract Doc Link 18243568 Disease Relevance 0.58 Pain Relevance 0.94

This study shows Avpr1b mRNA to be most prominent in the CA2 pyramidal neurons of the mouse and human HIP while receptor transcripts are also found in the paraventricular nucleus (PVN) and amygdala, albeit at a lower level.

Positive_regulation (prominent) of Avpr1b in pyramidal neurons associated with pyramidal cell, hippocampus and amygdala

11) Confidence 0.44 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0 Pain Relevance 0.15

Nevertheless, a number of studies utilising immunohistochemistry and in situ hybridisation histochemistry (ISHH) have shown that the Avpr1b is expressed centrally, while reverse transcription-polymerase chain reaction (RT-PCR) and functional studies have demonstrated Avpr1bs in a number of peripheral tissues (e.g.

Positive_regulation (demonstrated) of Avpr1bs

12) Confidence 0.41 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.33 Pain Relevance 0

In vitro studies using cells transiently transfected with a rat Avpr1b gene promoter sequence have identified regulatory GAGA repeats that influence Avpr1b gene transcription (Volpi et al. 2002).

Positive_regulation (sequence) of Avpr1b

13) Confidence 0.41 Published 2011 Journal Stress (Amsterdam, Netherlands) Section Body Doc Link PMC3016603 Disease Relevance 0.38 Pain Relevance 0.17

We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs).

Positive_regulation (increased) of AVPR1b associated with affective disorder

14) Confidence 0.30 Published 2004 Journal Mol. Psychiatry Section Abstract Doc Link 15094789 Disease Relevance 0.61 Pain Relevance 0.17

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