scholarly journals The Involvement of l-Arginine-Nitric Oxide-cGMP-ATP-Sensitive K+ Channel Pathway in Antinociception of BBHC, a Novel Diarylpentanoid Analogue, in Mice Model

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7431
Author(s):  
Hui Ming Ong ◽  
Ahmad Farhan Ahmad Azmi ◽  
Sze Wei Leong ◽  
Faridah Abas ◽  
Enoch Kumar Perimal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Channel Blocker ◽  
Antinociceptive Effect ◽  
Soluble Guanylyl Cyclase ◽  
K Channel ◽  
Mice Model ◽  
Chemically Induced ◽  
Pre Treatment ◽  
Oxide Synthase ◽  
Abdominal Constriction

The present study focuses on the possible involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway in the antinociceptive activity of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC) via a chemical nociceptive model in mice. The antinociceptive action of BBHC (1 mg/kg, i.p.) was attenuated by the intraperitoneal pre-treatment of l-arginine (a nitric oxide synthase precursor) and glibenclamide (an ATP-sensitive K+ channel blocker) in acetic acid-induced abdominal constriction tests. Interestingly, BBHC’s antinociception was significantly enhanced by the i.p. pre-treatment of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase (p < 0.05). Altogether, these findings suggest that the systemic administration of BBHC is able to establish a significant antinociceptive effect in a mice model of chemically induced pain. BBHC’s antinociception is shown to be mediated by the involvement of l-arginine-nitric oxide-cGMP-ATP-sensitive K+ channel pathway, without any potential sedative or muscle relaxant concerns.

Participation of the opioid receptor – nitric oxide – cGMP – K+ channel pathway in the peripheral antinociceptive effect of nalbuphine and buprenorphine in rats

2020 ◽  
Vol 98 (11) ◽  
pp. 753-762
Author(s):  
Mario I. Ortiz ◽  
Raquel Cariño-Cortés ◽  
Gilberto Castañeda-Hernández
Keyword(s):  
Nitric Oxide ◽  
Channel Blocker ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channel ◽  
Formalin Injection ◽  
Opioid Agonist ◽  
The Right

The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats (180–220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50–200 μg/paw) or buprenorphine (1–5 μg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (NG-nitro-l-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)), by the Kir6.1–2, ATP-sensitive K+ channel inhibitors (glibenclamide and glipizide), by the KCa2.1–3, small conductance Ca2+-activated K+ channel blocker (apamin), by the KCa1.1, large conductance Ca2+-activated K+ channel blocker (charybdotoxin), and by the KV, voltage-dependent K+ channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.

Effects of Hypoxic Acclimation, Muscle Strain and Contraction Frequency on Nitric Oxide-Mediated Myocardial Performance in Steelhead Trout (Oncorhynchus mykiss)

2021 ◽  
Author(s):  
Christian Carnevale ◽  
Douglas A. Syme ◽  
A. Kurt Gamperl
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Soluble Guanylyl Cyclase ◽  
Surprising Result ◽  
Muscle Strain ◽  
No Donor ◽  
Contraction Frequency ◽  
Mediated Effects ◽  
Oxide Synthase ◽  
Hypoxic Acclimation

Whether hypoxic acclimation influences nitric oxide (NO)-mediated control of fish cardiac function is not known. Thus, we measured the function / performance of myocardial strips from normoxia and hypoxia-acclimated (40% air saturation; ~ 8 kPa O2) trout at several frequencies (20 - 80 contractions min-1) and two muscle strain amplitudes (8 and 14%) when exposed to increasing concentrations of the NO donor sodium nitroprusside (SNP) (10-9 to 10-4 M). Further, we examined the influence of: 1) nitric oxide synthase (NOS) produced NO (by blocking NOS with 10-4 M L-NMMA); and 2) soluble guanylyl cyclase mediated, NOS-independent, NO effects (i.e., after blockade with 10-4 M ODQ), on myocardial contractility. Hypoxic acclimation increased twitch duration by 8-10% and decreased mass-specific net power by ~35%. However, hypoxic acclimation only had minor impacts on the effects of SNP and the two blockers on myocardial function. The most surprising result of this study was the degree to which contraction frequency and strain amplitude influenced NO-mediated effects on myocardial power. For example, at 8% strain 10-4 SNP resulted in a decrease in net power of ~30% at 20 min-1 but an increase of ~20% at 80 min-1, and this effect was magnified at 14% strain. This study: suggests that hypoxic acclimation has only minor effects on NO-mediated myocardial contractility in salmonids; is the first to report the highly frequency- and strain-dependent nature of NO effects on myocardial contractility in fishes; and supports previous work showing that NO effects on the heart (myocardium) are finely tuned spatio-temporally.

scholarly journals Synaptic Localization of Nitric Oxide Synthase and Soluble Guanylyl Cyclase in the Hippocampus

2002 ◽  
Vol 22 (20) ◽  
pp. 8961-8970 ◽  
Author(s):  
Alain Burette ◽  
Ulrike Zabel ◽  
Richard J. Weinberg ◽  
Harald H. H. W. Schmidt ◽  
Juli G. Valtschanoff
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Synaptic Localization ◽  
Oxide Synthase

TNF-alpha and IFN-gamma induce expression of nitric oxide synthase in cultured rat medullary interstitial cells

1995 ◽  
Vol 269 (2) ◽  
pp. F212-F217 ◽  
Author(s):  
K. S. Lau ◽  
O. Nakashima ◽  
G. R. Aalund ◽  
L. Hogarth ◽  
K. Ujiie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Nitric Oxide Synthase ◽  
Vascular Smooth Muscle ◽  
Guanylyl Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
Tnf Alpha ◽  
No Production ◽  
Ifn Gamma ◽  
Oxide Synthase

Cytokines increase the expression of the inducible (type II) nitric oxide synthase (NOS) in macrophages, liver, and renal epithelial cells. Previously, we found that cultured rat medullary interstitial cells (RMIC) contain high levels of soluble guanylyl cyclase. To determine whether these cells can also produce NO, we studied the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on NO production, NOS II mRNA, and NOS II protein expression. Both TNF-alpha and IFN-gamma, in the presence of a low concentration of the other cytokine, caused dose-dependent increases in NO production. Exposure to TNF-alpha and IFN-gamma stimulated the production of NOS II mRNA, as determined by Northern blotting. Restriction mapping of reverse transcription-polymerase chain reaction products indicated that normal cells contained macrophage NOS II, whereas cytokine-stimulated cells contained primarily vascular smooth muscle NOS II and some macrophage NOS II. The appearance of NOS II protein was demonstrated by Western blotting. RMIC cell guanosine 3',5'-cyclic monophosphate accumulation increased 129-fold in response to the cytokines. NOS inhibitors decreased nitrite production. We conclude that 1) TNF-alpha and IFN-gamma induce the expression of vascular smooth muscle NOS II and production of NO in RMIC, and 2) NO acts as an autocrine activator of the soluble guanylyl cyclase in RMIC.

Delayed stress-induced antinociceptive effect of nitric oxide synthase inhibition in the dentate gyrus of rats

2002 ◽  
Vol 74 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Marcela B Echeverry ◽  
Francisco S Guimarães ◽  
Marina A Oliveira ◽  
William A do Prado ◽  
Elaine A Del Bel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Dentate Gyrus ◽  
Antinociceptive Effect ◽  
Oxide Synthase

Central antinociceptive effect of tapentadol is increased by nitric oxide synthase inhibitors

2016 ◽  
Vol 27 (7) ◽  
pp. 606-614 ◽  
Author(s):  
Magdalena Bujalska-Zadrożny ◽  
Renata Wolińska ◽  
Anna Leśniak ◽  
Mariusz Sacharczuk
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Antinociceptive Effect ◽  
Nitric Oxide Synthase Inhibitors ◽  
Oxide Synthase
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