Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

다국어 초록 (Multilingual Abstract)

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents (Icap). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on Icap. Membrane-permeable cGMP analogs, 8-bromoguanosine 3’, 5’-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3’,5’-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on Icap. The PKG inhibitor KT5823 prevented the inhibition of Icap by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

참고문헌 (Reference)

1 Davis JB, "Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia" 405 : 183-187, 2000

2 Hao JX, "Treatment of a chronic allodynia-like response in spinally injured rats: effects of systemically administered nitric oxide synthase inhibitors" 66 : 313-319, 1996

3 Jin Y, "Thimerosal decreases TRPV1 activity by oxidation of extracellular sulfhydryl residues" 369 : 250-255, 2004

4 Koplas PA, "The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons" 17 : 3525-3537, 1997

5 Ferreira SH, "The molecular mechanism of action of peripheral morphine analgesia: stimulation of the cGMP system via nitric oxide release" 201 : 121-122, 1991

6 Tominaga M, "The cloned capsaicin receptor integrates multiple pain-producing stimuli" 21 : 531-543, 1998

7 Caterina MJ, "The capsaicin receptor : a heat-activated ion channel in the pain pathway" 389 : 816-824, 1997

8 Shim WS, "TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase" 27 : 2331-2337, 2007

9 Miyamoto T, "TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice" 4 : 7596-, 2009

10 Levine JD, "TRP channels: targets for the relief of pain" 1772 : 989-1003, 2007

11 Malmberg AB, "Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats" 54 : 291-300, 1993

12 Vyklický L, "Reducing agent dithiothreitol facilitates activity of the capsaicin receptor VR-1" 111 : 435-441, 2002

13 Campbell DL, "Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols" 108 : 277-293, 1996

14 Saito S, "Rat spinal cord neurons contain nitric oxide synthase" 59 : 447-456, 1994

15 Zhou XB, "Protein phosphatase 2A is essential for the activation of Ca2＋- activated K＋ currents by cGMP-dependent protein kinase in tracheal smooth muscle and Chinese hamster ovary cells" 271 : 19760-19767, 1996

16 White RE, "Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation" 361 : 263-266, 1993

17 Durate ID, "Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway" 186 : 289-293, 1990

18 Tousova K, "Oxidizing reagent copper-o-phenanthroline is an open channel blocker of the vanilloid receptor TRPV1" 47 : 273-285, 2004

19 Lauretti GR, "Oral ketamine and transdermal nitroglycerin as analgesic adjuvants to oral morphine therapy for cancer pain management" 90 : 1528-1533, 1999

20 Blaise GA, "Nitric oxide, cell signaling and cell death" 208 : 177-192, 2005

21 Thippeswamy T, "Nitric oxide, a biological double-faced janus--is this good or bad?" 21 : 445-458, 2006

22 Zhang X, "Nitric oxide synthase-like immunoreactivity in lumbar dorsal root ganglia and spinal cord of rat and monkey and effect of peripheral axotomy" 335 : 563-575, 1993

23 Dun NJ, "Nitric oxide synthase immunoreactivity in rat spinal cord" 147 : 217-220, 1992

24 Martínez-Ruiz A, "Nitric oxide signaling: classical, less classical, and nonclassical mechanisms" 51 : 17-29, 2011

25 Aley KO, "Nitric oxide signaling in pain and nociceptor sensitization in the rat" 18 : 7008-7014, 1998

26 Jian K, "Nitric oxide modulation of voltage-gated calcium current by S-nitrosylation and cGMP pathway in cultured rat hippocampal neurons" 359 : 481-485, 2007

27 Yoshimura N, "Nitric oxide modulates Ca2＋ channels in dorsal root ganglion neurons innervating rat urinary bladder" 86 : 304-311, 2001

28 Irwin C, "Nitric oxide inhibits platelet adhesion to collagen through cGMP-dependent and independent mechanisms: the potential role for S-nitrosylation" 20 : 478-486, 2009

29 Castel H, "Nitric oxide directly activates GABA(A) receptor function through a cGMP/protein kinase-independent pathway in frog pituitary melanotrophs" 13 : 695-705, 2001

30 Núñez L, "Nitric oxide blocks hKv1.5 channels by S-nitrosylation and by a cyclic GMP-dependent mechanism" 72 : 80-89, 2006

31 Renganathan M, "Nitric oxide blocks fast, slow, and persistent Na＋ channels in C-type DRG neurons by S-nitrosylation" 87 : 761-775, 2002

32 Lang RJ, "Nitric oxide and thiol reagent modulation of Ca2＋-activated K＋ (BKCa) channels in myocytes of the guinea-pig taenia caeci" 525 : 363-376, 2000

33 Guzik TJ, "Nitric oxide and superoxide in inflammation and immune regulation" 54 : 469-487, 2003

34 Yoshida T, "Nitric oxide activates TRP channels by cysteine S-nitrosylation" 2 : 596-607, 2006

35 이종주, "Nitric Oxide Modulation of GABAergic Synaptic Transmission in Mechanically Isolated Rat Auditory Cortical Neurons" 대한약리학회 13 (13): 461-467, 2009

36 Herring N, "NO-cGMP pathway increases the hyperpolarisation-activated current, If, and heart rate during adrenergic stimulation" 52 : 446-453, 2001

37 Almanza A, "Modulation of voltage-gated Ca2＋ current in vestibular hair cells by nitric oxide" 97 : 1188-1195, 2007

38 Han J, "Modulation of ATP-sensitive potassium channels by cGMP-dependent protein kinase in rabbit ventricular myocytes" AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 276 : 22140-22147, 2001

39 Moore PK, "L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse" 102 : 198-202, 1991

40 Przewłocki R, "Inhibition of nitric oxide synthase enhances morphine antinociception in the rat spinal cord" 53 : 1-5, 1993

41 Machelska H, "Inhibition of nitric oxide synthase enhances antinociception mediated by mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord" 282 : 977-984, 1997

42 Caterina MJ, "Impaired nociception and pain sensation in mice lacking the capsaicin receptor" 288 : 306-313, 2000

43 Haley JE, "Electrophysiological evidence for a role of nitric oxide in prolonged chemical nociception in the rat" 31 : 251-258, 1992

44 Ellershaw DC, "Dual modulation of swelling-activated chloride current by NO and NO donors in rabbit portal vein myocytes" 528 : 15-24, 2000

45 Ahern GP, "Direct actions of nitric oxide on rat neurohypophysial K＋ channels" 520 : 165-176, 1999

46 Fukao M, "Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072" 274 : 10927-10935, 1999

47 Oh U, "Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons" 16 : 1659-1667, 1996

48 Shin J, "Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia" National Academy of Sciences 99 (99): 10150-10155, 2002

49 Ferreira SH, "Blockade of hyperalgesia and neurogenic oedema by topical application of nitroglycerin" 217 : 207-209, 1992

50 Kawabata A, "Antinociceptive effect of L-arginine on the carrageenin-induced hyperalgesia of the rat: possible involvement of central opioidergic systems" 218 : 153-158, 1992

51 Harima A, "Analgesic effect of L-arginine in patients with persistent pain" 1 : 529-533, 1991

52 Lopshire JC, "Activation and recovery of the PGE2-mediated sensitization of the capsaicin response in rat sensory neurons" 78 : 3154-3164, 1997

53 Zhang N, "A proinflammatory chemokine, CCL3, sensitizes the heat-and capsaicin-gated ion channel TRPV1" 102 : 4536-4541, 2005

54 Roche AK, "A nitric oxide synthesis inhibitor (L-NAME) reduces licking behavior and Fos-labeling in the spinal cord of rats during formalin-induced inflammation" 66 : 331-341, 1996

55 Zsombok A, "A cGMP-dependent cascade enhances an L-type-like Ca2＋ current in identified snail neurons" 1032 : 70-76, 2005