Transient receptor potential vanilloid 4 (TRPV4) activation by arachidonic acid requires protein kinase A–mediated phosphorylation

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms20133271 ◽

2019 ◽

Vol 20 (13) ◽

pp. 3271 ◽

Cited By ~ 2

Author(s):

Kanako Miyano ◽

Seiji Shiraishi ◽

Koichiro Minami ◽

Yuka Sudo ◽

Masami Suzuki ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Mechanical Allodynia ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Adenosine Monophosphate ◽

Anchoring Protein ◽

Cold Hyperalgesia ◽

Transient Receptor ◽

Kinase A

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is not only involved in pain transmission, but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased the carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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Cilostazol Suppresses Angiotensin II–Induced Vasoconstriction via Protein Kinase A–Mediated Phosphorylation of the Transient Receptor Potential Canonical 6 Channel

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.110.221010 ◽

2011 ◽

Vol 31 (10) ◽

pp. 2278-2286 ◽

Cited By ~ 30

Author(s):

Kinue Nishioka ◽

Motohiro Nishida ◽

Marina Ariyoshi ◽

Zhong Jian ◽

Shota Saiki ◽

...

Keyword(s):

Angiotensin Ii ◽

Protein Kinase ◽

Protein Kinase A ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Transient Receptor Potential Canonical ◽

Transient Receptor ◽

Kinase A

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Modulation of Transient Receptor Potential Vanilloid 4-Mediated Membrane Currents and Synaptic Transmission by Protein Kinase C

Molecular Pain ◽

10.1186/1744-8069-5-5 ◽

2009 ◽

Vol 5 ◽

pp. 1744-8069-5-5 ◽

Cited By ~ 45

Author(s):

De-Shou Cao ◽

Shuang-Quan Yu ◽

Louis S Premkumar

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Synaptic Transmission ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Membrane Currents ◽

Transient Receptor Potential Vanilloid ◽

Kinase C ◽

Transient Receptor

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Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

Cellular Physiology and Biochemistry ◽

10.1159/000487350 ◽

2018 ◽

Vol 45 (3) ◽

pp. 1084-1096 ◽

Cited By ~ 5

Author(s):

Mengwen Qi ◽

Chunfeng Wu ◽

Zhouqing Wang ◽

Li Zhou ◽

Chen Men ◽

...

Keyword(s):

Protein Kinase ◽

Transient Receptor Potential ◽

Pyramidal Neurons ◽

Receptor Potential ◽

Chloride Ion ◽

Transient Receptor Potential Vanilloid ◽

Patch Clamp Recording ◽

Hippocampal Pyramidal Neurons ◽

Protein Levels ◽

Transient Receptor

Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs) and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4) is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly) and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET) increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047) and GlyR (strychnine), indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC) (BIM II or D-sphingosine) or calcium/calmodulin-dependent protein kinase II (CaMKII) (KN-62 or KN-93) antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv.) injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

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