scholarly journals Follistatin induction by nitric oxide through cyclic GMP: a tightly regulated signaling pathway that controls myoblast fusion

2006 ◽  
Vol 172 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Addolorata Pisconti ◽  
Silvia Brunelli ◽  
Monica Di Padova ◽  
Clara De Palma ◽  
Daniela Deponti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cyclic Guanosine Monophosphate ◽  
Myoblast Fusion ◽  
Guanosine Monophosphate ◽  
Time Dependent ◽  
Secreted Protein ◽  
Skeletal Myoblast ◽  
Cgmp Signaling ◽  
Endogenous Nitric Oxide

The mechanism of skeletal myoblast fusion is not well understood. We show that endogenous nitric oxide (NO) generation is required for myoblast fusion both in embryonic myoblasts and in satellite cells. The effect of NO is concentration and time dependent, being evident only at the onset of differentiation, and direct on the fusion process itself. The action of NO is mediated through a tightly regulated activation of guanylate cyclase and generation of cyclic guanosine monophosphate (cGMP), so much so that deregulation of cGMP signaling leads to a fusion-induced hypertrophy of satellite-derived myotubes and embryonic muscles, and to the acquisition of fusion competence by myogenic precursors in the presomitic mesoderm. NO and cGMP induce expression of follistatin, and this secreted protein mediates their action in myogenesis. These results establish a hitherto unappreciated role of NO and cGMP in regulating myoblast fusion and elucidate their mechanism of action, providing a direct link with follistatin, which is a key player in myogenesis.

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

2011 ◽  
Vol 89 (2) ◽  
pp. 89-95 ◽  
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.

scholarly journals NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway contribute to the antidepressant-like effect of Yueju pill in mice

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wei Wang ◽  
Tong Zhou ◽  
Rong Jia ◽  
Hailou Zhang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Forced Swim Test ◽  
Specific Inhibitor ◽  
Tail Suspension Test ◽  
Cyclic Guanosine Monophosphate ◽  
Nmda Receptor Antagonist ◽  
No Synthase ◽  
Guanosine Monophosphate ◽  
Immobility Time ◽  
Cgmp Signaling

Abstract The present study aims to evaluate the involvement of N-methyl-d-aspartate receptor and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) system in antidepressant-like effects of Yueju pill (YJ), a Chinese herbal medicine. The immobility time in tail suspension test (TST) and forced swim test (FST) was used to assess the antidepressant effects. Prior administration of L-arginine (750 mg/kg, intraperitoneal [i.p.]), a NO synthase substrate that enhances NO signaling or sildenafil (5 mg/kg, i.p.), a phosphodiesterase 5 inhibitor that enhances cGMP, blunted the antidepressant-like activity of YJ (2.7 g/kg, i.g.). Co-treatment of ineffective dose of YJ (1.35 g/kg, i.g.) with one of the reagents that suppress the NO/cGMP signaling, including methylene blue (10 mg/kg, i.p.), an inhibitor of NO synthase; 7-NI (7-nitroinidazole, 30 mg/kg, i.p.), an nNOS specific inhibitor; L-NAME (10 mg/kg, i.p.), a non-specific inhibitor of NO synthase; and MK-801 (0.05 mg/kg, i.p.), an NMDA receptor antagonist, reduced the immobility time in TST and FST, compared with those in vehicle or single drug treatment groups. Neither above drugs alone or co-administrated with YJ affected locomotor activity or anxiety behavior in open field test. Thus, our results suggest that the antidepressant-like action of YJ may depend on the inhibition of NMDA/NO/cGMP pathway.

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.

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.

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