INT7833

Context Info Confidence 0.70 First Reported 1984 Last Reported 2010 Negated 1 Speculated 1 Reported most in Abstract Documents 33 Total Number 36 Disease Relevance 8.54 Pain Relevance 34.21

extracellular space (Cck) extracellular region (Cck) DNA binding (Cck)

Anatomy Link Frequency spinal cord 3 plasma 2 pyramidal cell 1 brain 1 central nervous system 1 Cck (Mus musculus)

Pain Link Frequency Relevance Heat Cholecystokinin 418 100.00 Opioid 85 100.00 Morphine 79 100.00 Enkephalin 51 100.00 Dynorphin 38 100.00 agonist 38 100.00 Neuropeptide 17 100.00 nMDA receptor 12 100.00 Delta opioid receptors 4 99.98 antagonist 110 99.72

Disease Link Frequency Relevance Heat Convulsion 3 99.98 Critical Illness 24 99.12 Eating Disorder 3 98.72 Sleep Disorders 6 98.36 Neuropathic Pain 41 98.02 Appetite Loss 14 97.92 Cancer 228 97.36 Stress 11 96.12 INFLAMMATION 48 94.76 Hyperalgesia 15 93.44

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Event

Anatomy

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Disease term

In this work we have shown, by in vivo binding experiments, that the endogenous enkephalins, protected from degrading enzymes by mixed inhibitors such as kelatorphan and N-[(R,S)-2-benzyl-3-[(S)-2-amino-4-methylthiobutyldithio]-1-oxo pro pyl]- L-phenylalanine benzyl ester (RB 101), a systemically active prodrug, modulate CCK release in mouse brain, leading to an overall increase in the extracellular levels of CCK.

Positive_regulation (increase) of CCK in brain associated with enkephalin and cholecystokinin

1) Confidence 0.70 Published 1992 Journal J. Neurochem. Section Abstract Doc Link 1357099 Disease Relevance 0 Pain Relevance 0.75

RESULTS: In the plantar analgesia test the latency of hind paw withdrawal was significantly increased in CCK(2) receptor deficient mice compared to wild-type (+/+) littermates.

Positive_regulation (increased) of CCK in paw

2) Confidence 0.69 Published 2003 Journal Psychopharmacology (Berl.) Section Body Doc Link 12545332 Disease Relevance 0.08 Pain Relevance 0

The antinociceptive activity of SNF9007 was not a result of the activation of CCK receptors, as treatment with either CCK-A or CCK-B receptor antagonist was ineffective in blocking SNF9007 antinociception.

Positive_regulation (activation) of CCK associated with antinociception, antagonist and antinociceptive

3) Confidence 0.56 Published 1994 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 8182541 Disease Relevance 0 Pain Relevance 1.30

Previous work indicates that the antianalgesic action of pentobarbital and neurotensin administered intracerebroventricularly in mice arises from activation of a descending system to release cholecystokinin (CCK) in the spinal cord where CCK is known to antagonize morphine analgesia.

Positive_regulation (activation) of CCK in spinal cord associated with cholecystokinin, analgesia, morphine and spinal cord

4) Confidence 0.50 Published 1999 Journal Proc. Soc. Exp. Biol. Med. Section Abstract Doc Link 10193446 Disease Relevance 0 Pain Relevance 0.99

Previous work indicates that the antianalgesic action of pentobarbital and neurotensin administered intracerebroventricularly in mice arises from activation of a descending system to release cholecystokinin (CCK) in the spinal cord where CCK is known to antagonize morphine analgesia.

Positive_regulation (activation) of cholecystokinin in spinal cord associated with cholecystokinin, analgesia, morphine and spinal cord

5) Confidence 0.50 Published 1999 Journal Proc. Soc. Exp. Biol. Med. Section Abstract Doc Link 10193446 Disease Relevance 0 Pain Relevance 0.98

In contrast, 3R[+]-N-[2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-benzodiazepin-3-yl ]-N'- [3-methyl-phenyl]urea (L365,260), a selective CCKB receptor antagonist, blocked the action of CCK4(30-33) and SNF 9007 (phase I), and also antagonized CCK8(s), though to a lesser degree.

Positive_regulation (action) of CCK4 associated with antagonist

6) Confidence 0.50 Published 1994 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 8113956 Disease Relevance 0 Pain Relevance 0.30

These data demonstrate that the blockade of endogenous CCK actions leads to morphine sensitization probably through both CCK receptors.

Positive_regulation (leads) of CCK associated with morphine

7) Confidence 0.50 Published 2001 Journal Peptides Section Abstract Doc Link 11457524 Disease Relevance 0 Pain Relevance 1.20

Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers.

Positive_regulation (induce) of CCK in mossy fibers associated with dynorphin and enkephalin

8) Confidence 0.50 Published 1988 Journal J. Neurosci. Section Title Doc Link 2898512 Disease Relevance 0.28 Pain Relevance 0.78

The stimulation of CCK(A) receptors seems to increase the release of endogenous enkephalins.

Positive_regulation (stimulation) of CCK associated with enkephalin and cholecystokinin

9) Confidence 0.50 Published 1999 Journal Eur Neuropsychopharmacol Section Abstract Doc Link 10082226 Disease Relevance 0 Pain Relevance 1.41

In these animals, which were tested for antinociception on the 5th day, tolerance to the drug (3, 6 and 9 mg/kg s.c.) was also decreased by caerulein, CCK-8 but not unsulfated CCK-8.

Neg (not) Positive_regulation (unsulfated) of CCK-8 associated with antinociception and tolerance

10) Confidence 0.50 Published 1994 Journal Eur. J. Pharmacol. Section Abstract Doc Link 8206114 Disease Relevance 0 Pain Relevance 1.09

It is concluded that the cholecystokinin agonist caerulein potentiated the morphine response by stimulation of cholecystokinin-A and/or cholecystokinin-B receptors.

Positive_regulation (stimulation) of cholecystokinin associated with agonist, cholecystokinin and morphine

11) Confidence 0.50 Published 1997 Journal Gen. Pharmacol. Section Abstract Doc Link 9013214 Disease Relevance 0 Pain Relevance 1.63

It is concluded that the cholecystokinin agonist caerulein potentiated the morphine response by stimulation of cholecystokinin-A and/or cholecystokinin-B receptors.

Positive_regulation (stimulation) of cholecystokinin associated with agonist, cholecystokinin and morphine

12) Confidence 0.50 Published 1997 Journal Gen. Pharmacol. Section Abstract Doc Link 9013214 Disease Relevance 0 Pain Relevance 1.63

Gene expression analysis revealed an up-regulation of CCK(2) receptor gene in the lumbar spinal cord and mesolimbic area in wild-type mice in response to stress.

Positive_regulation (up-regulation) of CCK in spinal cord associated with stress, cholecystokinin and spinal cord

13) Confidence 0.50 Published 2008 Journal Eur. J. Neurosci. Section Abstract Doc Link 18412633 Disease Relevance 0.37 Pain Relevance 1.82

Cholecystokinin2 (CCK2) receptor-deficient mice were used to analyze the in vivo function of CCK2 receptor and especially the incidence of this gene invalidation on enkephalinergic and dopaminergic systems.

Spec (analyze) Positive_regulation (function) of CCK2

14) Confidence 0.49 Published 2001 Journal Neurosci. Lett. Section Abstract Doc Link 11403953 Disease Relevance 0.07 Pain Relevance 0.30

As in other experimental paradigms, CCK(A) and CCK(B) receptor stimulation appears to have opposite effects in modulating opioidergic activity.

Positive_regulation (stimulation) of CCK

15) Confidence 0.49 Published 1996 Journal Eur. J. Pharmacol. Section Abstract Doc Link 9016909 Disease Relevance 0 Pain Relevance 0.70

As in other experimental paradigms, CCK(A) and CCK(B) receptor stimulation appears to have opposite effects in modulating opioidergic activity.

Positive_regulation (stimulation) of CCK

16) Confidence 0.49 Published 1996 Journal Eur. J. Pharmacol. Section Abstract Doc Link 9016909 Disease Relevance 0 Pain Relevance 0.71

The existence of regulatory loops between both systems has been proposed, and the physiological antagonism between CCK, through activation of CCK2 receptors, and endogenous opioid systems has been demonstrated.

Positive_regulation (activation) of CCK associated with endogenous opioid and cholecystokinin

17) Confidence 0.49 Published 2003 Journal Drugs Today Section Abstract Doc Link 14702135 Disease Relevance 0.06 Pain Relevance 1.19

The results suggest that activation of CCK-A receptors by BDNL leads to antinociceptive responses indirectly mediated by stimulation of mu-opioid receptors by endogenous enkephalins.

Positive_regulation (activation) of CCK associated with mu opioid receptor, enkephalin, antinociceptive and cholecystokinin

18) Confidence 0.49 Published 1993 Journal Neurosci. Lett. Section Abstract Doc Link 8247353 Disease Relevance 0 Pain Relevance 1.22

These findings again suggest that the effect of CART peptide was pronounced through activation of CCK-A receptor and point to satiety-related sedation.

Positive_regulation (activation) of CCK associated with sleep disorders and cholecystokinin

19) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2587474 Disease Relevance 0.10 Pain Relevance 0.76

The action of CCK on CART expression was shown to be mediated by activation of protein kinase C and cAMP response element binding protein (CREB) and was inhibited by orexigenic ghrelin [25].

Positive_regulation (action) of CCK associated with kinase c and cholecystokinin

20) Confidence 0.48 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2587474 Disease Relevance 0.15 Pain Relevance 0.70

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