INT166591

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.30
First Reported 2006
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 4
Total Number 22
Disease Relevance 0.69
Pain Relevance 12.18

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

nucleus (CALCA, DCLK3) cytoplasm (CALCA, DCLK3) extracellular space (CALCA)
aging (CALCA) extracellular region (CALCA) intracellular (CALCA)
CALCA (Homo sapiens)
DCLK3 (Homo sapiens)
DCLK3 - L34A (2)
Pain Link Frequency Relevance Heat
Calcitonin gene-related peptide 3748 100.00 Very High Very High Very High
Neuropeptide 573 100.00 Very High Very High Very High
Potency 269 100.00 Very High Very High Very High
agonist 215 94.92 High High
Migraine 25 93.84 High High
headache 22 93.12 High High
antagonist 211 86.00 High High
Disease Link Frequency Relevance Heat
Migraine Disorders 25 93.84 High High
Neuroblastoma 19 74.00 Quite High
Disease 57 58.48 Quite High
Stroke 19 7.80 Low Low
Increased Venous Pressure Under Development 38 5.00 Very Low Very Low Very Low
Heart Disease 19 5.00 Very Low Very Low Very Low
Hypertension 19 5.00 Very Low Very Low Very Low
Reperfusion Injury 19 5.00 Very Low Very Low Very Low
Heat Stress Disorders 19 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The calcitonin receptor-like receptor (CLR) associates with the accessory protein RAMP1 to form a receptor for the neuropeptide calcitonin gene-related peptide (CGRP).
CGRP Binding (associates) of CLR associated with neuropeptide and calcitonin gene-related peptide
1) Confidence 0.30 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20188075 Disease Relevance 0.16 Pain Relevance 0.73
The calcitonin receptor-like receptor (CLR) associates with the accessory protein RAMP1 to form a receptor for the neuropeptide calcitonin gene-related peptide (CGRP).
gene-related peptide Binding (associates) of CLR associated with neuropeptide and calcitonin gene-related peptide
2) Confidence 0.26 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20188075 Disease Relevance 0.16 Pain Relevance 0.72
The calcitonin receptor-like receptor (CLR) associates with the accessory protein RAMP1 to form a receptor for the neuropeptide calcitonin gene-related peptide (CGRP).
CGRP Binding (associates) of CLR associated with neuropeptide and calcitonin gene-related peptide
3) Confidence 0.22 Published 2010 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 20188075 Disease Relevance 0.16 Pain Relevance 0.73
Consequently, it is reasonable to assume that interactions of CGRP-F37 with the mature CLR-RAMP1 heterodimer would necessitate a more complex relationship in order to account for the high affinity binding associated with the loss of this C-terminal peptide residue.
CGRP-F37 Binding (heterodimer) of CLR associated with calcitonin gene-related peptide
4) Confidence 0.18 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0.07 Pain Relevance 0.74
To address this idea, a minimized molecular model of a 13 amino acid CLR N-terminal domain fragment interacting with CGRP-F37 is put forward in figure 5.
CGRP-F37 Binding (interacting) of CLR associated with calcitonin gene-related peptide
5) Confidence 0.18 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0.06 Pain Relevance 0.48
This is contrary to the 6- to 8-fold loss of CGRP binding affinity for these same CLR mutations.
CGRP Binding (affinity) of CLR associated with calcitonin gene-related peptide
6) Confidence 0.18 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.72
These IC50 values were used to calculate the equilibrium dissociation constants (Ki) of competing CGRP ligands for specific CLR-RAMP1 heterodimer binding sites expressed on HEK293T cells using the method of Cheng and Prusoff [28].


CGRP Binding (ligands) of CLR associated with calcitonin gene-related peptide
7) Confidence 0.16 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.37
However, this affinity loss was no different from wild type receptor when CGRP(1–36) or CGRP(1–19) were used to compete for specific L24A, L34A or L24A,L34A mutant CLR binding sites on transiently transfected HEK293T-RAMP1 cells.
CGRP Binding (compete) of CLR (L34A) associated with calcitonin gene-related peptide
8) Confidence 0.16 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.55
This binding property difference of truncated C-terminus peptide ligands versus CGRP for leucine mutants and wild type receptor proteins, strongly advocates CLR L24 and L34 as important binding contacts for CGRP-F37.
CGRP-F37 Binding (contacts) of CLR L24 associated with calcitonin gene-related peptide
9) Confidence 0.16 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.51
A model illustrating this interaction of specific CGRP domains with the CLR-RAMP1 heterodimer (i.e., mature CGRP receptor) is presented in figure 1.
CGRP Binding (interaction) of CLR associated with calcitonin gene-related peptide
10) Confidence 0.16 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.44
This study is the first to describe specific amino acids on the CLR N-terminus domain postulated to selectively interact with the C-terminal phenylalaninamide of CGRP, previously shown to impart the high affinity relationship of the neuropeptide with the mature CGRP receptor.
CGRP Binding (interact) of CLR associated with neuropeptide and calcitonin gene-related peptide
11) Confidence 0.15 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.55
However, this affinity loss was no different from wild type receptor when CGRP(1–36) or CGRP(1–19) were used to compete for specific L24A, L34A or L24A,L34A mutant CLR binding sites on transiently transfected HEK293T-RAMP1 cells.
CGRP Binding (compete) of CLR (L34A) associated with calcitonin gene-related peptide
12) Confidence 0.14 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.55
Therefore, compared to wild type CLR, binding affinity losses of these peptide ligands for the leucine CLR mutations suggests that L24 and L34 are significant binding contacts with CGRP-F37.
CGRP-F37 Binding (contacts) of CLR associated with calcitonin gene-related peptide
13) Confidence 0.14 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.70
In addition, this CGRP affinity loss is no different when both leucines are modified in the same receptor protein, indicating that there is not a synergistic relationship between these CLR residues for CGRP binding.
CGRP Binding (binding) of CLR associated with calcitonin gene-related peptide
14) Confidence 0.13 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.45
For example, a purified CLR N-terminal domain overexpressed in E. coli was able to specifically bind 125I-CGRP and could displace this same radiolabeled peptide from a membrane preparation containing native CGRP receptors [25].
CGRP Binding (bind) of CLR associated with calcitonin gene-related peptide
15) Confidence 0.13 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.33
Based on results from this study, a fundamental model of CGRP interaction with these N-terminus CLR leucine residues is brought forward.
CGRP Binding (interaction) of CLR associated with calcitonin gene-related peptide
16) Confidence 0.13 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0.06 Pain Relevance 0.44
Moreover, this explanation for changes in CGRP binding affinity with no differences in potency for mutant versus wild type CLR supports the concept of two distinct neuropeptide domains responsible for receptor binding and agonism [31].
CGRP Neg (no) Binding (affinity) of CLR associated with neuropeptide, potency and calcitonin gene-related peptide
17) Confidence 0.12 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.89
Specific to the CLR, deletion of an 18 amino acid region of the receptor N-terminal domain resulted in a significant loss of 125I-CGRP binding when co-expressed in mammalian cells with RAMP1 [26].
CGRP Binding (binding) of CLR associated with calcitonin gene-related peptide
18) Confidence 0.12 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.46
In summary, we have characterized specific leucine residues on the CLR membrane protein that participate in the high affinity CGRP binding mediated by the C-terminal phenylalaninamide of the neuropeptide.
CGRP Binding (binding) of CLR associated with neuropeptide and calcitonin gene-related peptide
19) Confidence 0.12 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.40
In summary, we have characterized specific leucine residues on the CLR membrane protein that participate in the high affinity CGRP binding mediated by the C-terminal phenylalaninamide of the neuropeptide.
CGRP Binding (binding) of CLR associated with neuropeptide and calcitonin gene-related peptide
20) Confidence 0.12 Published 2006 Journal BMC Pharmacol Section Body Doc Link PMC1525162 Disease Relevance 0 Pain Relevance 0.40

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox