Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

Abstract

Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein.

Original languageEnglish
Title of host publicationIon Channels DownUnder
EditorsDominic P Geraghty, Lachlan D Rash
Place of PublicationCambridge MA USA
PublisherAcademic Press
Chapter4
Pages117-139
Number of pages23
Volume79
ISBN (Print)9780128104132
DOIs
Publication statusPublished - 2017

Publication series

NameAdvances in Pharmacology
PublisherAcademic Press
Volume79
ISSN (Print)1054-3589

Keywords

  • Calcium signaling
  • Edema
  • Glia
  • Immune cell
  • Inflammation
  • Ion channel
  • Nociception
  • Transient receptor potential
  • TRPV4
  • Vascular

Cite this

Rajasekhar, P., Poole, D. P., & Veldhuis, N. A. (2017). Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. In D. P. Geraghty, & L. D. Rash (Eds.), Ion Channels DownUnder (Vol. 79, pp. 117-139). (Advances in Pharmacology; Vol. 79). Cambridge MA USA: Academic Press. Advances in Pharmacology https://doi.org/10.1016/bs.apha.2017.03.002
Rajasekhar, Pradeep ; Poole, Daniel P. ; Veldhuis, Nicholas A. / Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. Ion Channels DownUnder. editor / Dominic P Geraghty ; Lachlan D Rash. Vol. 79 Cambridge MA USA : Academic Press, 2017. pp. 117-139 (Advances in Pharmacology). (Advances in Pharmacology).
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keywords = "Calcium signaling, Edema, Glia, Immune cell, Inflammation, Ion channel, Nociception, Transient receptor potential, TRPV4, Vascular",
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Rajasekhar, P, Poole, DP & Veldhuis, NA 2017, Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. in DP Geraghty & LD Rash (eds), Ion Channels DownUnder. vol. 79, Advances in Pharmacology, vol. 79, Academic Press, Cambridge MA USA, Advances in Pharmacology, pp. 117-139. https://doi.org/10.1016/bs.apha.2017.03.002

Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. / Rajasekhar, Pradeep; Poole, Daniel P.; Veldhuis, Nicholas A.

Ion Channels DownUnder. ed. / Dominic P Geraghty; Lachlan D Rash. Vol. 79 Cambridge MA USA : Academic Press, 2017. p. 117-139 (Advances in Pharmacology; Vol. 79).

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

TY - CHAP

T1 - Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes

AU - Rajasekhar, Pradeep

AU - Poole, Daniel P.

AU - Veldhuis, Nicholas A.

PY - 2017

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N2 - Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein.

AB - Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein.

KW - Calcium signaling

KW - Edema

KW - Glia

KW - Immune cell

KW - Inflammation

KW - Ion channel

KW - Nociception

KW - Transient receptor potential

KW - TRPV4

KW - Vascular

UR - http://www.scopus.com/inward/record.url?scp=85018797829&partnerID=8YFLogxK

U2 - 10.1016/bs.apha.2017.03.002

DO - 10.1016/bs.apha.2017.03.002

M3 - Chapter (Book)

SN - 9780128104132

VL - 79

T3 - Advances in Pharmacology

SP - 117

EP - 139

BT - Ion Channels DownUnder

A2 - Geraghty, Dominic P

A2 - Rash, Lachlan D

PB - Academic Press

CY - Cambridge MA USA

ER -

Rajasekhar P, Poole DP, Veldhuis NA. Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes. In Geraghty DP, Rash LD, editors, Ion Channels DownUnder. Vol. 79. Cambridge MA USA: Academic Press. 2017. p. 117-139. (Advances in Pharmacology). (Advances in Pharmacology). https://doi.org/10.1016/bs.apha.2017.03.002