Nitric Oxide Potentiates cAMP-Gated Cation Current in Feeding Neurons of Pleurobranchaea californica Independent of cAMP and cGMP Signaling Pathways

Critical roles for nitric oxide (NO) in regulating cell and tissue physiology are broadly appreciated, but aspects remain to be explored. In the mollusk Pleurobranchaea, NO synthase activity is high in CNS ganglia containing motor networks for feeding and locomotion, where a cAMP-gated cation current ( INa,cAMP) is also prominent in many neurons. We examined effects of NO on INa,cAMP using voltage-clamp methods developed to analyze cAMP signaling in the live neuron, focusing on the identified metacerebral giant neuron of the feeding network. NO donors enhanced the INa,cAMP response to injected cAMP by an averaged 85%. In dose-response measures, NO increased the current stimulated by cAMP injection without altering either apparent cAMP binding affinity or cooperativity of current activation. NO did not detectably alter levels of native cAMP or synthesis or degradation rates as observable in both current saturation and decay rate of INa,cAMP responses to cAMP injection. NO actions were not exerted by cGMP signaling, as they were not mimicked by cGMP analogue nor blocked by inhibitors of guanylate cyclase and protein kinase G. NO potentiation of INa,cAMP was broadly distributed among many other neurons of the feeding motor network in the buccal ganglion. However, NO did not affect a second type of INa,cAMP found in locomotor neurons of the pedal ganglia. These results suggest that NO acts through a novel mechanism to regulate the gain of cAMP-dependent neuromodulatory pathways that activate INa,cAMP and may thereby affect the set points of feeding network excitability and reactivity to exogenous input.

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Nitric Oxide Potentiates cAMP-Gated Cation Current by Intracellular Acidification in Feeding Neurons of Pleurobranchaea

Journal of Neurophysiology ◽

10.1152/jn.00021.2010 ◽

2010 ◽

Vol 104 (2) ◽

pp. 742-745 ◽

Cited By ~ 5

Author(s):

Kurt Potgieter ◽

Nathan G. Hatcher ◽

Rhanor Gillette ◽

Catherine R. McCrohan

Keyword(s):

Nitric Oxide ◽

Signaling Pathways ◽

Intracellular Ph ◽

Camp Signaling ◽

Intracellular Acidification ◽

Ph Indicator ◽

Intracellular Injection ◽

Cation Current ◽

Motor Network ◽

Important Regulator

A pH-sensitive cAMP-gated cation current ( INa,cAMP) is widely distributed in neurons of the feeding motor networks of gastropods. In the sea slug Pleurobranchaea this current is potentiated by nitric oxide (NO), which itself is produced by many feeding neurons. The action of NO is not dependent on either cGMP or cAMP signaling pathways. However, we found that NO potentiation of INa,cAMP in the serotonergic metacerebral cells could be blocked by intracellular injection of MOPS buffer (pH 7.2). In neurons injected with the pH indicator BCECF, NO induced rapid intracellular acidification to several tenths of a pH unit. Intracellular pH has not previously been identified as a specific target of NO, but in this system NO modulation of INa,cAMP via pHi may be an important regulator of the excitability of the feeding motor network.

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Nitric Oxide Potentiates cAMP-Gated Cation Current in Feeding Neurons of Pleurobranchaea californica Independent of cAMP and cGMP Signaling Pathways

Journal of Neurophysiology ◽

10.1152/jn.0815.2005 ◽

2006 ◽

Vol 95 (5) ◽

pp. 3219-3227 ◽

Cited By ~ 1

Author(s):

N. G. Hatcher

Keyword(s):

Nitric Oxide ◽

Signaling Pathways ◽

Pleurobranchaea Californica ◽

Cation Current ◽

Cgmp Signaling ◽

Camp And Cgmp

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MicroRNA-155 Amplifies Nitric Oxide/cGMP Signaling and Impairs Vascular Angiotensin II Reactivity in Septic Shock

Critical Care Medicine ◽

10.1097/ccm.0000000000003296 ◽

2018 ◽

Vol 46 (9) ◽

pp. e945-e954 ◽

Cited By ~ 6

Author(s):

Francisco Vasques-Nóvoa ◽

Tiago L. Laundos ◽

Rui J. Cerqueira ◽

Catarina Quina-Rodrigues ◽

Ricardo Soares-dos-Reis ◽

...

Keyword(s):

Nitric Oxide ◽

Septic Shock ◽

Angiotensin Ii ◽

Cgmp Signaling

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The nitric oxide–cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-109 ◽

2011 ◽

Vol 89 (2) ◽

pp. 89-95 ◽

Cited By ~ 22

Author(s):

Ercan Ozdemir ◽

Ihsan Bagcivan ◽

Nedim Durmus ◽

Ahmet Altun ◽

Sinan Gursoy

Keyword(s):

Nitric Oxide ◽

Analgesic Effect ◽

Soluble Guanylate Cyclase ◽

Morphine Tolerance ◽

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Albino Rats ◽

Tail Flick ◽

Analgesic Effects ◽

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

European Journal of Pharmacology ◽

10.1016/s0014-2999(03)02117-4 ◽

2003 ◽

Vol 476 (1-2) ◽

pp. 107-113 ◽

Cited By ~ 19

Author(s):

Tamás Csont ◽

Csaba Csonka ◽

Péter Kovács ◽

Gábor Jancsó ◽

Péter Ferdinandy

Keyword(s):

Nitric Oxide ◽

Sensory Neurons ◽

Cgmp Signaling

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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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Action-potential broadening and endogenously sustained bursting are substrates of command ability in a feeding neuron of Pleurobranchaea

Journal of Neurophysiology ◽

10.1152/jn.1980.43.3.669 ◽

1980 ◽

Vol 43 (3) ◽

pp. 669-685 ◽

Cited By ~ 68

Author(s):

R. Gillette ◽

M. U. Gillette ◽

W. J. Davis

Keyword(s):

Action Potential ◽

Action Potentials ◽

Motor Output ◽

Buccal Ganglion ◽

Short Pulses ◽

Motor Network ◽

Single Axon ◽

Network Output ◽

Bilateral Pair ◽

Potential Activity

1. The ventral white cells (VWC's) of the buccal ganglion of Pleurobranchaea, so named for their position and color, are a bilateral pair of neuron somata. Each sends a single axon out its contralateral stomatogastric nerve and has a dendritic field originating close to the soma. 2. The vwcs exhibit spontaneous episodes of prolonged depolarization (duration 1--4 min) accompanied by repetitive action-potential activity and separated by regular intervals of 3--30 min. Such prolonged burst episodes can be triggered by short pulses of depolarizing current. During the repetitive activity of the spontaneous bursts or that driven by imposed depolarization, the action potentials progressively broaden to 5--16 times their initial duration. 3. During spontaneous bursting or activity driven by imposed depolarization, the cyclic motor output of the feeding network is initiated or accelerated with a latency corresponding with the development of appreciable VWC spike broadening. When broadening of antidromic VWC spikes is suppressed by imposed hyperpolarization of the soma, the frequency of feeding cycles is significantly lower than when broadened spikes are allowed to develop. When trains of spikes are driven by depolarizing current, the motor output of the feeding network is not initiated until the VWC spikes have broadened to a repeatable "threshold" duration, regardless of the intensity of the depolarizing current. 4. The endogenous production of prolonged burst episodes, triggered by depolarizing current pulses, and progressive spike broadening can be demonstrated in the surgically isolated VWC soma. 5. The paired VWCs are strongly electrically coupled and display highly synchronous activity. They receive synaptic inputs from many previously identified interneurons of the feeding network and are thus reciprocally coupled within the network. 6. These results demonstrate that the capacity of this neuron to generate broadened action potentials during repetitive activity confers the ability to command coordinated motor-network output. The appropriate repetitive activity can be produced endogenously in the form of prolonged bursts of spikes.

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