Actions of nitric oxide-generating sodium nitroprusside in myenteric plexus of guinea pig small intestine

1993 ◽  
Vol 265 (5) ◽  
pp. G887-G893 ◽  
Author(s):  
K. Tamura ◽  
M. Schemann ◽  
J. D. Wood
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Guinea Pig ◽  
Sodium Nitroprusside ◽  
Myenteric Plexus ◽  
Membrane Properties ◽  
Dependent Manner ◽  
Membrane Excitability ◽  
Concentration Dependent Manner ◽  
Myenteric Neurons

Sodium nitroprusside (NaNP) was used as a donor of nitric oxide (NO) to investigate actions of NO on electrical and synaptic behavior of single myenteric neurons in guinea pig small intestine. NaNP (10 microM-1 mM) did not affect resting membrane properties of the neurons, except for an occasional decrease in input resistance and hyperpolarization attributable to suppression of excitatory transmitter release. NaNP did not alter fast nicotinic neurotransmission but suppressed noncholinergic slow excitatory postsynaptic potentials (slow EPSPs) in a concentration-dependent manner. Pretreatment with either methylene blue or oxyhemoglobin reduced the inhibitory action of NaNP on the slow EPSPs. Slow EPSP-like responses to microejected substance P or 5-hydroxytryptamine were unaffected by NaNP. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, did not affect resting membrane excitability or excitatory synaptic events in any of the myenteric neurons. The results suggest that NO may not be released extensively as a neurotransmitter at synapses within the myenteric plexus. If myenteric neurons are exposed to NO released from nonneural sources, then the principal action is expected to be presynaptic inhibition of slow synaptic excitation.

Dipyridamole Potentiates the Endothelium-Dependent and -Independent Vasomotion in Isolated Human Small Arteries

1996 ◽  
Vol 1 (3) ◽  
pp. 203-209 ◽  
Author(s):  
Roberto Pedrinelli
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Adenosine Receptor ◽  
Guanosine Monophosphate ◽  
Muscarinic Agonist ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adenosine Receptor Agonist ◽  
Synthase Inhibitor

Background To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery. Methods and Results Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A2-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole. Conclusion Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A2 adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

scholarly journals Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon

2009 ◽  
Vol 296 (4) ◽  
pp. G823-G832 ◽  
Author(s):  
Guijun Fei ◽  
Yu-Zhong Wang ◽  
Sumei Liu ◽  
Hong-Zhen Hu ◽  
Guo-Du Wang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Guinea Pig ◽  
Short Circuit ◽  
Enteric Neurons ◽  
Resting Membrane Potential ◽  
Small Intestinal Mucosa ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Mucosal Secretion ◽  
Stimulation Of

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current ( Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1–3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1–3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1–3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed ( P < 0.001) lubiprostone-evoked Isc. Lubiprostone, in the presence of tetrodotoxin, enhanced carbachol-evoked Isc. The cholinergic component, but not the putative vasoactive intestinal peptide component, of neural responses to electrical field stimulation was enhanced by lubiprostone. Application of any of the prostaglandins, E2, F2, or I2, evoked depolarization of the resting membrane potential in enteric neurons. Unlike the prostaglandins, lubiprostone did not alter the electrical behavior of enteric neurons. Exposure to the histamine H2 receptor agonists increased basal Isc followed by persistent cyclical increases in Isc. Lubiprostone increased the peak amplitude of the dimaprit-evoked cycles.

scholarly journals Homeoprotein OTX1 and OTX2 involvement in rat myenteric neuron adaptation after DNBS-induced colitis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8442
Author(s):  
Michela Bistoletti ◽  
Giovanni Micheloni ◽  
Nicolò Baranzini ◽  
Annalisa Bosi ◽  
Andrea Conti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Small Intestine ◽  
Nitric Oxide Synthase ◽  
Myenteric Plexus ◽  
Distal Colon ◽  
Myeloperoxidase Activity ◽  
Myenteric Neurons ◽  
Protein Levels ◽  
Oxide Synthase

Background Inflammatory bowel diseases are associated with remodeling of neuronal circuitries within the enteric nervous system, occurring also at sites distant from the acute site of inflammation and underlying disturbed intestinal functions. Homeoproteins orthodenticle OTX1 and OTX2 are neuronal transcription factors participating to adaptation during inflammation and underlying tumor growth both in the central nervous system and in the periphery. In this study, we evaluated OTX1 and OTX2 expression in the rat small intestine and distal colon myenteric plexus after intrarectal dinitro-benzene sulfonic (DNBS) acid-induced colitis. Methods OTX1 and OTX2 distribution was immunohistochemically investigated in longitudinal muscle myenteric plexus (LMMP)-whole mount preparations. mRNAs and protein levels of both OTX1 and OTX2 were evaluated by qRT-PCR and Western blotting in LMMPs. Results DNBS-treatment induced major gross morphology and histological alterations in the distal colon, while the number of myenteric neurons was significantly reduced both in the small intestine and colon. mRNA levels of the inflammatory markers, TNFα, pro-IL1β, IL6, HIF1α and VEGFα and myeloperoxidase activity raised in both regions. In both small intestine and colon, an anti-OTX1 antibody labeled a small percentage of myenteric neurons, and prevalently enteric glial cells, as evidenced by co-staining with the glial marker S100β. OTX2 immunoreactivity was present only in myenteric neurons and was highly co-localized with neuronal nitric oxide synthase. Both in the small intestine and distal colon, the number of OTX1- and OTX2-immunoreactive myenteric neurons significantly increased after DNBS treatment. In these conditions, OTX1 immunostaining was highly superimposable with inducible nitric oxide synthase in both regions. OTX1 and OTX2 mRNA and protein levels significantly enhanced in LMMP preparations of both regions after DNBS treatment. Conclusions These data suggest that colitis up-regulates OTX1 and OTX2 in myenteric plexus both on site and distantly from the injury, potentially participating to inflammatory-related myenteric ganglia remodeling processes involving nitrergic transmission.

The action of substance P on neurons of the myenteric plexus of the guinea-pig small intestine

1979 ◽  
Vol 206 (1163) ◽  
pp. 191-208 ◽  
Keyword(s):  
Small Intestine ◽  
Substance P ◽  
Guinea Pig ◽  
Myenteric Plexus ◽  
Reversal Potential ◽  
Membrane Depolarization ◽  
Extracellular Potassium ◽  
Membrane Hyperpolarization ◽  
Myenteric Neurons

Extracellular and intracellular recordings were made in vitro from single neurons of the myenteric plexus of the guinea-pig small intestine. Synthetic substance P was applied to the neurons by means of the perfusing solution or by electrophoresis from micropipettes. Extracellular recording showed that substance P (100 pM-30 nM), applied by perfusion, increased the firing rate of myenteric neurons. Intracellular recording indicated that perfusion with substance P caused a dose-dependent membrane depolarization which was unaffected by hexamethonium, hyoscine, naloxone or baclofen. The depolarization was also evoked by electrophoretic application of substance P. It was associated with an increase in membrane resistance, augmented by membrane depolarization and reduced by membrane hyperpolarization. The relation between the substance P reversal potential and the logarithm of the extracellular potassium concentration was linear with a slope of 54 mV/log 10 [K + ], which indicates that substance P inactivates the resting potassium conductance of the myenteric neurons. This effect on ion conductance is the same as that of an unknown substance that mediates slow synaptic excitations with the myenteric plexus.

Immunochemical visualization of cyclic AMP in myenteric neurons of guinea-pig small intestine+

2001 ◽  
Vol 120 (5) ◽  
pp. A683-A683
Author(s):  
J GUZMAN ◽  
S SHARP ◽  
J YU ◽  
F MCMORRIS ◽  
A WIEMELT ◽  
...  
Keyword(s):  
Small Intestine ◽  
Cyclic Amp ◽  
Guinea Pig ◽  
Myenteric Neurons

Inducible nitric oxide synthase augments injury elicited by oxidative stress in rat cardiac myocytes

1998 ◽  
Vol 274 (1) ◽  
pp. C245-C252 ◽  
Author(s):  
Junsuke Igarashi ◽  
Masashi Nishida ◽  
Shiro Hoshida ◽  
Nobushige Yamashita ◽  
Hiroaki Kosaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Cardiac Myocytes ◽  
Myocardial Injury ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
No Donor ◽  
Oxide Synthase ◽  
Gpx Activity

The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined. Interleukin-1β induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS,l-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso- N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2(0.1 mM, 1 h). Inhibition of iNOS with Nω-nitro-l-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.

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