Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis that activation of the transient receptor potential vanilloid 4 (TRPV4) channel conveys a hypotensive effect that is enhanced during salt load, male Wistar rats fed a normal-sodium (0.5%) or high-sodium (HS; 4%) diet for 3 weeks were given 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a specific TRPV4 activator, in the presence or absence of capsazepine, a selective TRPV1 blocker, ruthenium red, a TRPV4 blocker, or TRPV4 small hairpin RNA that selectively knockdowns TRPV4. 4 alpha-PDD (1, 2.5, or 5 mg/kg IV) dose-dependently decreased mean arterial pressure (P<0.05). HS enhanced 4 alpha-PDD-induced depressor effects as well as 4 alpha-PDD-mediated release of calcitonin gene-related peptide and substance P (P<0.001). Ruthenium red markedly blunted (P<0.001), whereas capsazepine slightly attenuated (P<0.05) 4 alpha-PDD-induced depressor effects in HS and normal-sodium diet rats. Ruthenium red alone increased baseline mean arterial pressure in both HS and normal-sodium diet rats with a greater magnitude in the former (P<0.05). Western blot analysis showed that HS increased TRPV4 expression in dorsal root ganglia and mesenteric arteries (P<0.05) but not the renal cortex and medulla. Gene-silencing approach revealed that TRPV4 small hairpin RNA downregulated TRPV4 expression leading to blunted 4 alpha-PDD-induced hypotension (P<0.05). Thus, TRPV4 activation decreases blood pressure in rats given a normal-sodium diet. HS enhances TRPV4 expression in sensory nerves/mesenteric arteries and TRPV4-mediated depressor effects and calcitonin gene-related peptide/substance P release such that HS causes a greater increase in blood pressure when TRPV4 is blocked. Our data indicate that TRPV4 activation may constitute a compensatory mechanism in preventing salt-induced increases in blood pressure.
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PMID:Salt intake augments hypotensive effects of transient receptor potential vanilloid 4: functional significance and implication. 1907 88

The aim of this study is to investigate the effect of microtubule depolymerization by colchicine on hyperalgesia mediated by transient receptor potential vanilloid 4 (TRPV4) in a neuropathic pain model of chronic compression of the dorsal root ganglion (DRG) (hereafter termed CCD) in rat. Intrathecal administration of microtubule-depolymerizing agent, colchicine, attenuated the activated effect of 4alpha-phorbol 12, 13-didecanoate (4alpha-PDD, TRPV4 specific agonist) on mechanical and thermal hyperalgesia in CCD rats. This observation is in agreement with our in vitro experiments with DRG cells that showed a significant attenuation of 4alpha-PDD-activated Ca(2+)-influx and substance P (SP) release with the colchicine treatment. We conclude that microtubule depolymerization by colchicine can regulate pain sensitivity by depressing the hyperalgesia mediated by TRPV4.
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PMID:Role of colchicine-induced microtubule depolymerization in hyperalgesia via TRPV4 in rats with chronic compression of the dorsal root ganglion. 2407 78