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Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis.

Assas BM, Pennock JI, Miyan JA - Front Neurosci (2014)

Bottom Line: This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems.However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals.But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body.

View Article: PubMed Central - PubMed

Affiliation: Translational Medicine, Faculty of Medical and Human Sciences, The University of Manchester Manchester, UK ; Department of Immunology, Faculty of Applied Sciences, King Abdulaziz University Jeddah, Saudi Arabia.

ABSTRACT
The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

No MeSH data available.


Related in: MedlinePlus

Pathways of CGRP release via TRPV1 activation. TRPV1 is activated by many external factors associated with pain but also regular sensation below pain thresholds. These include the well characterized responses to heat, pH, and damage, as well as to toxins, immune challenges and membrane potential changes brought about by physiological and pathological processes. Endogenous and/or intracellular activation can also occur through the actions of PIP2 and Anandomide. Any activation of TRPV1 results in release of CGRP from the neuron. This released CGRP then acts on its specific receptor on cells immediately adjacent to the neuron, which in the case of sensory c fibers can be lymphocytes, DCs, mast cells, macrophages or cells within the hemopoietic microenvironment of the bone marrow (not shown). The range of activities stimulated by CGRP are listed below each cell type.
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Figure 1: Pathways of CGRP release via TRPV1 activation. TRPV1 is activated by many external factors associated with pain but also regular sensation below pain thresholds. These include the well characterized responses to heat, pH, and damage, as well as to toxins, immune challenges and membrane potential changes brought about by physiological and pathological processes. Endogenous and/or intracellular activation can also occur through the actions of PIP2 and Anandomide. Any activation of TRPV1 results in release of CGRP from the neuron. This released CGRP then acts on its specific receptor on cells immediately adjacent to the neuron, which in the case of sensory c fibers can be lymphocytes, DCs, mast cells, macrophages or cells within the hemopoietic microenvironment of the bone marrow (not shown). The range of activities stimulated by CGRP are listed below each cell type.

Mentions: CGRP is released in response to activation of TRPV1 in both the nervous and immune systems. In the nervous system, TRPV1 is expressed along the entire length of the sensory c fiber neurons, from the periphery to the somata in the CNS (Szallasi, 1995). These neurons innervate every organ and tissue in the body (Buck and Burks, 1986; Holzer, 1991; Szallasi and Blumberg, 1999). Although a key exogenous ligand for TRPV1 is capsaicin, TRPV1 is also activated by a range of other endogenous agonists including heat (>43°C) (Caterina et al., 1997; Tominaga et al., 1998), protons (~pH 4.5) (Vyklicky et al., 1998; Jordt et al., 2000), lipids like anandamide (Olah et al., 2001), phosphatidylinositol(4,5)-biphosphate (PIP2) (Chuang et al., 2001), and voltage (Gunthorpe et al., 2000) (summarized in Figure 1). Heat and low pH activate TRPV1 by distinct molecular recognition sites (Jordt et al., 2000). Additionally, TRPV1 has been suggested to be a mechanosensitive receptor in mediating nociceptive signals; for example TRPV1 deficient mice exhibit reduced sensitivity to post colorectal distension compared to controls (Jones et al., 2005) adding an interesting physiological element to TRPV1 activation. In rats, sensory vanilloid receptor-bearing nerves are classed as peptidergic and/or purinergic (Guo et al., 1999). Peptidergic nerves express TRPV1 and co-express neuropeptides whilst purinergic nerves express TRPV1 and co-express an adenosine triphosphate (ATP) gated ion-channel known as P2X3 (Yiangou et al., 2001).


Calcitonin gene-related peptide is a key neurotransmitter in the neuro-immune axis.

Assas BM, Pennock JI, Miyan JA - Front Neurosci (2014)

Pathways of CGRP release via TRPV1 activation. TRPV1 is activated by many external factors associated with pain but also regular sensation below pain thresholds. These include the well characterized responses to heat, pH, and damage, as well as to toxins, immune challenges and membrane potential changes brought about by physiological and pathological processes. Endogenous and/or intracellular activation can also occur through the actions of PIP2 and Anandomide. Any activation of TRPV1 results in release of CGRP from the neuron. This released CGRP then acts on its specific receptor on cells immediately adjacent to the neuron, which in the case of sensory c fibers can be lymphocytes, DCs, mast cells, macrophages or cells within the hemopoietic microenvironment of the bone marrow (not shown). The range of activities stimulated by CGRP are listed below each cell type.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924554&req=5

Figure 1: Pathways of CGRP release via TRPV1 activation. TRPV1 is activated by many external factors associated with pain but also regular sensation below pain thresholds. These include the well characterized responses to heat, pH, and damage, as well as to toxins, immune challenges and membrane potential changes brought about by physiological and pathological processes. Endogenous and/or intracellular activation can also occur through the actions of PIP2 and Anandomide. Any activation of TRPV1 results in release of CGRP from the neuron. This released CGRP then acts on its specific receptor on cells immediately adjacent to the neuron, which in the case of sensory c fibers can be lymphocytes, DCs, mast cells, macrophages or cells within the hemopoietic microenvironment of the bone marrow (not shown). The range of activities stimulated by CGRP are listed below each cell type.
Mentions: CGRP is released in response to activation of TRPV1 in both the nervous and immune systems. In the nervous system, TRPV1 is expressed along the entire length of the sensory c fiber neurons, from the periphery to the somata in the CNS (Szallasi, 1995). These neurons innervate every organ and tissue in the body (Buck and Burks, 1986; Holzer, 1991; Szallasi and Blumberg, 1999). Although a key exogenous ligand for TRPV1 is capsaicin, TRPV1 is also activated by a range of other endogenous agonists including heat (>43°C) (Caterina et al., 1997; Tominaga et al., 1998), protons (~pH 4.5) (Vyklicky et al., 1998; Jordt et al., 2000), lipids like anandamide (Olah et al., 2001), phosphatidylinositol(4,5)-biphosphate (PIP2) (Chuang et al., 2001), and voltage (Gunthorpe et al., 2000) (summarized in Figure 1). Heat and low pH activate TRPV1 by distinct molecular recognition sites (Jordt et al., 2000). Additionally, TRPV1 has been suggested to be a mechanosensitive receptor in mediating nociceptive signals; for example TRPV1 deficient mice exhibit reduced sensitivity to post colorectal distension compared to controls (Jones et al., 2005) adding an interesting physiological element to TRPV1 activation. In rats, sensory vanilloid receptor-bearing nerves are classed as peptidergic and/or purinergic (Guo et al., 1999). Peptidergic nerves express TRPV1 and co-express neuropeptides whilst purinergic nerves express TRPV1 and co-express an adenosine triphosphate (ATP) gated ion-channel known as P2X3 (Yiangou et al., 2001).

Bottom Line: This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems.However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals.But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body.

View Article: PubMed Central - PubMed

Affiliation: Translational Medicine, Faculty of Medical and Human Sciences, The University of Manchester Manchester, UK ; Department of Immunology, Faculty of Applied Sciences, King Abdulaziz University Jeddah, Saudi Arabia.

ABSTRACT
The question of how the neural and immune systems interact in host defense is important, integrating a system that senses the whole body with one that protects. Understanding the mechanisms and routes of control could produce novel and powerful ways of promoting and enhancing normal functions as well as preventing or treating abnormal functions. Fragmentation of biological research into specialities has resulted in some failures in recognizing and understanding interactions across different systems and this is most striking across immunology, hematology, and neuroscience. This reductionist approach does not allow understanding of the in vivo orchestrated response generated through integration of all systems. However, many factors make the understanding of multisystem cross-talk in response to a threat difficult, for instance the nervous and immune systems share communication molecules and receptors for a wide range of physiological signals. But, it is clear that physical, hard-wired connections exist between the two systems, with the key link involving sensory, unmyelinated nerve fibers (c fibers) containing the neuropeptide calcitonin gene-related peptide (CGRP), and modified macrophages, mast cells and other immune and host defense cells in various locations throughout the body. In this review we will therefore focus on the induction of CGRP and its key role in the neuroimmune axis.

No MeSH data available.


Related in: MedlinePlus