scholarly journals Methanolic Extract ofClinacanthus nutansExerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Hafiz Abdul Rahim ◽  
Zainul Amiruddin Zakaria ◽  
Mohd Hijaz Mohd Sani ◽  
Maizatul Hasyima Omar ◽  
Yusnita Yakob ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Antinociceptive Effect ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
Clinacanthus Nutans ◽  
Synthase Inhibitor

The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract ofClinacanthus nutans(Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p<0.05) antinociceptive response in all nociceptive models with the recordedED50value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed byL-arginine (L-arg; a nitric oxide [NO] precursor), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract’s antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.

scholarly journals Cyclic Guanosine Monophosphate Modulates Locomotor Acceleration Induced by Nitric Oxide but not Serotonin in Clione limacina Central Pattern Generator Swim Interneurons

2020 ◽  
Author(s):  
Thomas J Pirtle ◽  
Richard A Satterlie
Keyword(s):  
Nitric Oxide ◽  
Central Pattern Generator ◽  
Guanylyl Cyclase ◽  
Signal Transduction Pathway ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Pattern Generator ◽  
Guanosine Monophosphate ◽  
Cellular Changes ◽  
Clione Limacina

Abstract Typically, the marine mollusk, Clione limacina, exhibits a slow, hovering locomotor gait to maintain its position in the water column. However, the animal exhibits behaviorally relevant locomotor swim acceleration during escape response and feeding behavior. Both nitric oxide and serotonin mediate this behavioral swim acceleration. In this study, we examine the role that the second messenger, cGMP, plays in mediating nitric oxide and serotonin-induced swim acceleration. We observed that the application of an analog of cGMP or an activator of soluble guanylyl cyclase increased fictive locomotor speed recorded from Pd-7 interneurons of the animal’s locomotor central pattern generator. Moreover, inhibition of soluble guanylyl cyclase decreased fictive locomotor speed. These results suggest that basal levels of cGMP are important for slow swimming and that increased production of cGMP mediates swim acceleration in Clione. Because nitric oxide has its effect through cGMP signaling and because we show herein that cGMP produces cellular changes in Clione swim interneurons that are consistent with cellular changes produced by serotonin application, we hypothesize that both nitric oxide and serotonin function via a common signal transduction pathway that involves cGMP. Our results show that cGMP mediates nitric oxide-induced but not serotonin-induced swim acceleration in Clione.

Nitric oxide donor stimulated increase of cyclic GMP in the goldfish retina

2001 ◽  
Vol 18 (6) ◽  
pp. 849-856 ◽  
Author(s):  
WILLIAM H. BALDRIDGE ◽  
ANDY J. FISCHER
Keyword(s):  
Nitric Oxide ◽  
Optic Nerve ◽  
Ganglion Cells ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Nitric Oxide Donor ◽  
No Donor ◽  
Intracellular Signalling Pathway ◽  
Teleost Retina

Nitric oxide (NO) activates soluble guanylyl cyclase (sGC) and the resulting increase in cyclic guanosine monophosphate (cGMP) is an important intracellular signalling pathway in the vertebrate retina. Immunocytochemical detection of cGMP following exposure to NO donors has proven an effective method of identifying cells that express sGC. While such an approach has proven useful for the study of several vertebrate retinas, it has not been applied to the well-characterized teleost retina. Therefore, in the present study, we have applied this approach to the retina of the goldfish (Carassius auratus). In the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), incubation of goldfish eyecups in Ringer's solution containing (±)-S-nitroso-N-acetylpenicillamine (SNAP) increased cGMP-like immunoreactivity (cG-ir) in bipolar, horizontal, amacrine, and ganglion cells and in ganglion cell axons and optic nerve. Weak labeling was observed in horizontal cells but no change in cG-ir was noted within photoreceptors. The NO donor-stimulated increases of cG-ir in horizontal, bipolar, amacrine, and ganglion cells are consistent with known physiological effects of NO on these neurons. The physiological significance of NO action at the level of optic nerve is not known. The lack of an effect of SNAP on cG-ir in photoreceptors was unexpected, as there are known physiological actions of NO, mediated by cGMP, on these neurons. Although this may be due to insufficient sensitivity of immunolabeling, this result may indicate a difference between isoforms of sGC or cGMP PDE in these neurons, compared to neurons where exogenous NO increased cG-ir.

scholarly journals Endothelin in health and disease

2004 ◽  
Vol 4 (3) ◽  
pp. 31-34 ◽  
Author(s):  
Emina Nakaš-Ićindić ◽  
Asija Začiragić ◽  
Almira Hadžović ◽  
Nešina Avdagić
Keyword(s):  
Nitric Oxide ◽  
Amino Acids ◽  
Calcium Ions ◽  
Potential Role ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Health And Disease ◽  
Endothelin 3 ◽  
Stimulation Of

Endothelin is a recently discovered peptide composed of 21 amino acids. There are three endothelin isomers: endothelin -1 (ET-1), endothelin -2 (ET-2) and endothelin - 3 (ET-3). In humans and animals levels of ET-1, ET-2, ET-3 and big endothelin in blood range from 0,3 to 3 pg/ml. ET-1, ET-2 and ET-3 act by binding to receptors. Two main types of the receptors for endothelins exist and they are referred to as A and B type receptors. Different factors can stimulate or inhibit production of endothelin by endothelial cells. Mechanical stimulation of endothehum, thrombin, calcium ions, epinephrine, angiotensin II, vasopressin, dopamine, cytokines, growth factors stimulate the production of endothelin whereas nitric oxide, cyclic guanosine monophosphate, atrial natriuretic peptide, prostacyclin, bradykinin inhibit its production. Endothelins have different physiological roles in human body but at the same time their actions are involved in the pathogenesis of many diseases.The aim of this review was to present some of, so far, the best studied physiological roles of endothelin and to summarize evidence supporting the potential role of ET in the pathogenesis of certain diseases.

scholarly journals Nitric Oxide-cGMP Signaling in Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1055-1068
Author(s):  
Ehsan Ataei Ataabadi ◽  
Keivan Golshiri ◽  
Annika Jüttner ◽  
Guido Krenning ◽  
A.H. Jan Danser ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Drug Targets ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Protein Kinase G ◽  
Current Status ◽  
Systemic Hypertension ◽  
Pharmacological Intervention ◽  
Cgmp Signaling

For the treatment of systemic hypertension, pharmacological intervention in nitric oxide-cyclic guanosine monophosphate signaling is a well-explored but unexploited option. In this review, we present the identified drug targets, including oxidases, mitochondria, soluble guanylyl cyclase, phosphodiesterase 1 and 5, and protein kinase G, important compounds that modulate them, and the current status of (pre)clinical development. The mode of action of these compounds is discussed, and based upon this, the clinical opportunities. We conclude that drugs that directly target the enzymes of the nitric oxide-cyclic guanosine monophosphate cascade are currently the most promising compounds, but that none of these compounds is under investigation as a treatment option for systemic hypertension.

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