Nitric oxide upregulates microglia phagocytosis and increases transient receptor potential vanilloid type 2 channel expression on the plasma membrane

Glia ◽  
2019 ◽  
Vol 67 (12) ◽  
pp. 2294-2311 ◽  
Author(s):  
Matthew J. E. Maksoud ◽  
Vasiliki Tellios ◽  
Dong An ◽  
Yun‐Yan Xiang ◽  
Wei‐Yang Lu
Keyword(s):  
Nitric Oxide ◽  
Plasma Membrane ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Channel Expression ◽  
Transient Receptor

scholarly journals Analgesic Effects of Lipid Raft Disruption by Sphingomyelinase and Myriocin via Transient Receptor Potential Vanilloid 1 and Transient Receptor Potential Ankyrin 1 Ion Channel Modulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Ádám Horváth ◽  
Maja Payrits ◽  
Anita Steib ◽  
Boglárka Kántás ◽  
Tünde Biró-Süt ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Lipid Raft ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Membrane Microdomains ◽  
Neuronal Cultures ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Sensitization ◽  
Transient Receptor

Transient Receptor Potential (TRP) Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) cation channels are expressed in nociceptive primary sensory neurons, and integratively regulate nociceptor and inflammatory functions. Lipid rafts are liquid-ordered plasma membrane microdomains rich in cholesterol, sphingomyelin and gangliosides. We earlier showed that lipid raft disruption inhibits TRPV1 and TRPA1 functions in primary sensory neuronal cultures. Here we investigated the effects of sphingomyelinase (SMase) cleaving membrane sphingomyelin and myriocin (Myr) prohibiting sphingolipid synthesis in mouse pain models of different mechanisms. SMase (50 mU) or Myr (1 mM) pretreatment significantly decreased TRPV1 activation (capsaicin)-induced nocifensive eye-wiping movements by 37 and 41%, respectively. Intraplantar pretreatment by both compounds significantly diminished TRPV1 stimulation (resiniferatoxin)-evoked thermal allodynia developing mainly by peripheral sensitization. SMase (50 mU) also decreased mechanical hyperalgesia related to both peripheral and central sensitizations. SMase (50 mU) significantly reduced TRPA1 activation (formalin)-induced acute nocifensive behaviors by 64% in the second, neurogenic inflammatory phase. Myr, but not SMase altered the plasma membrane polarity related to the cholesterol composition as shown by fluorescence spectroscopy. These are the first in vivo results showing that sphingolipids play a key role in lipid raft integrity around nociceptive TRP channels, their activation and pain sensation. It is concluded that local SMase administration might open novel perspective for analgesic therapy.

scholarly journals Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats

2019 ◽  
pp. 219-231 ◽  
Author(s):  
A. Boudaka ◽  
M. Al-Suleimani ◽  
I. Al-Lawati ◽  
H. Baomar ◽  
S. Al-Siyabi
Keyword(s):  
Nitric Oxide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Mesenteric Arteries ◽  
Transient Receptor Potential Vanilloid ◽  
Positive Staining ◽  
Hypertensive Rats ◽  
Transient Receptor ◽  
Endothelial Nitric Oxide ◽  
Trpv4 Channel

The endothelium contributes to the maintenance of vasodilator tone by releasing endothelium-derived relaxing factors, including nitric oxide (NO). In hypertension, endothelial nitric oxide synthase (eNOS) produces less NO and could be one of the contributing factors to the increased peripheral vascular resistance. Agonist-induced Ca(2+) entry is essential for the activation of eNOS. The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca(2+)-permeant cation channel, is expressed in the endothelial cells and involved in the regulation of vascular tone. The present study aimed to investigate the role of TRPV4 channel in endothelium-dependent NO-mediated relaxation of the resistance artery in hypertensive rats. Using a wire myograph, relaxation response to the TRPV4 activator, 4alpha-phorbol-12,13-didecanoate (4alphaPDD) was assessed in mesenteric arteries obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Compared to WKY, SHR demonstrated a significantly attenuated 4alphaPDD-induced endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the endothelium of mesenteric artery sections in both WKY and SHR. Furthermore, TRPV4 mRNA and protein expressions in SHR were significantly lower than their expression levels in WKY rats. We conclude that 4alphaPDD-induced endothelium-dependent NO-mediated vasorelaxation is reduced in SHR and downregulation of TRPV4 could be one of the contributing mechanisms.

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