Capsaicin-sensitive sensory neurons regulate myocardial nitric oxide and cGMP signaling

Although the phenomenon of opioid tolerance has been widely investigated, neither opioid nor nonopioid mechanisms are completely understood. The aim of the present study was to investigate the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the development of morphine-induced analgesia tolerance. The study was carried out on male Wistar albino rats (weighing 180–210 g; n = 126). To develop morphine tolerance, animals were given morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), BAY 41-2272, S-nitroso-N-acetylpenicillamine (SNAP), NG-nitro-l-arginine methyl ester (L-NAME), and morphine were considered at 15 or 30 min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests (n = 6 in each study group). The results showed that YC-1 and BAY 41-2272, a NO-independent activator of soluble guanylate cyclase (sGC), significantly increased the development and expression of morphine tolerance, and L-NAME, a NO synthase (NOS) inhibitor, significantly decreased the development of morphine tolerance. In conclusion, these data demonstrate that the nitric oxide–cGMP signal pathway plays a pivotal role in developing tolerance to the analgesic effect of morphine.

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H2S-induced HCO3− secretion in the rat stomach – Involvement of nitric oxide, prostaglandins, and capsaicin-sensitive sensory neurons

Nitric Oxide ◽

10.1016/j.niox.2014.11.001 ◽

2015 ◽

Vol 46 ◽

pp. 157-164 ◽

Cited By ~ 9

Author(s):

Koji Takeuchi ◽

Fumitaka Ise ◽

Kento Takahashi ◽

Eitaro Aihara ◽

Shusaku Hayashi

Keyword(s):

Nitric Oxide ◽

Sensory Neurons ◽

Rat Stomach

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Nitric oxide at a low concentration protects murine macrophage RAW264 cells against nitric oxide-induced death via cGMP signaling pathway

British Journal of Pharmacology ◽

10.1038/sj.bjp.0705206 ◽

2003 ◽

Vol 139 (1) ◽

pp. 28-34 ◽

Cited By ~ 24

Author(s):

Y Yoshioka ◽

A Yamamuro ◽

S Maeda

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Murine Macrophage ◽

Low Concentration ◽

Cgmp Signaling

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Gastroprotective Effect of Serjania erecta Radlk (Sapindaceae): Involvement of Sensory Neurons, Endogenous Nonprotein Sulfhydryls, and Nitric Oxide

Journal of Medicinal Food ◽

10.1089/jmf.2008.0269 ◽

2009 ◽

Vol 12 (6) ◽

pp. 1411-1415 ◽

Cited By ~ 13

Author(s):

Ana Paula Corrêa Castelo Branco Nap Arruda ◽

Roberta Gomes Coelho ◽

Neli Kika Honda ◽

Catharine Ferrazoli ◽

Arnildo Pott ◽

...

Keyword(s):

Nitric Oxide ◽

Sensory Neurons ◽

Gastroprotective Effect

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Involvement of the nitric oxide-cyclic GMP pathway in the desensitization of bradykinin responses of cultured rat sensory neurons

Neuron ◽

10.1016/0896-6273(92)90170-i ◽

1992 ◽

Vol 9 (2) ◽

pp. 315-324 ◽

Cited By ~ 60

Author(s):

Daniel S. McGehee ◽

Michael F. Goy ◽

Gerry S. Oxford

Keyword(s):

Nitric Oxide ◽

Sensory Neurons ◽

Cyclic Gmp

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Neuronal Nitric Oxide Synthase mRNA Upregulation in Rat Sensory Neurons after Spinal Nerve Ligation: Lack of a Role in Allodynia Development

Journal of Neuroscience ◽

10.1523/jneurosci.19-21-09201.1999 ◽

1999 ◽

Vol 19 (21) ◽

pp. 9201-9208 ◽

Cited By ~ 69

Author(s):

Z. David Luo ◽

S. R. Chaplan ◽

B. P. Scott ◽

D. Cizkova ◽

N. A. Calcutt ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Sensory Neurons ◽

Neuronal Nitric Oxide Synthase ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Oxide Synthase

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Abstract 178: Volume Overload Induced by Mitral Regurgitation Alters Spatial Regulation of Nitric Oxide/Reactive Nitrogen Species Signaling

Circulation Research ◽

10.1161/res.111.suppl_1.a178 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Yuchuan Liu ◽

Abdelkarim Sabri ◽

Louis Dell'Italia ◽

Victor Rizzo ◽

Emily J Tsai

Keyword(s):

Nitric Oxide ◽

Mitral Regurgitation ◽

Lipid Raft ◽

Reactive Nitrogen Species ◽

Volume Overload ◽

Nitrogen Species ◽

Spatial Regulation ◽

Cgmp Signaling ◽

Eccentric Hypertrophy ◽

Lipid Raft Microdomains

Volume-overload (VO), as seen in regurgitant valvular disease, large myocardial infarction, and severe cardiac systolic dysfunction, triggers eccentric hypertrophy. Given that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) modulate cardiomyocyte hypertrophy, apoptosis, and cardioprotection, differential regulation of these signals may distinguish eccentric from the more commonly studied concentric hypertrophy. We recently showed that pressure-overload (PO) induces relocalization and oxidation of the NO receptor soluble guanylyl cyclase (sGC), thereby diminishing cyclase activity and cGMP cardioprotection. The effects of volume-overload on NO and cGMP signaling are unknown. We tested the hypothesis that VO induces relocalization but not oxidation of sGC, thereby disrupting spatial regulation of NO-cGMP signaling without depressing cyclase activity. Volume-overload was established by chordal rupture-induced mitral regurgitation in dogs. We compared intracellular localization and activity of sGC in VO and control LVs (N=5 per group). Both sGC subunits were detected within and outside of caveolae-enriched lipid raft microdomains (Cav3+LR). In VO hearts, sGCβ1 fell in expression by nearly 50% and relocalized away from Cav3+LR to non-lipid raft microdomains (NLR). Despite VO-induced sGCβ1 changes, overall NO-stimulated sGC activity was preserved. An enhanced response to heme/NO-independent sGC activator BAY 60-2770 suggested that a subset of sGC was heme-oxidized in VO hearts, though to a much lesser degree than in PO hearts. As in PO hearts, Cav3+LR appear to protect sGC from heme-oxidation in VO hearts. Initial study of downstream reactive nitrogen species (RNS) and cGMP signaling supported our theory that VO altered spatial regulation of NO-cGMP signaling. Also, a trend towards increased overall tyrosine-nitration, predominantly within NLR, was observed in VO hearts. Volume-overload shifted cardiac NO-cGMP signaling from Cav3+LR to NLR microdomains without depressing NO/heme-dependent sGC activation. These findings suggest that differential spatial regulation of NO/RNS signaling, rather than simply increased RNS signaling, might drive the distinct molecular pathophysiology of eccentric hypertrophy.

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