scholarly journals Adiponectin Exerts Peripheral Inhibitory Effects on the Mouse Gastric Smooth Muscle through the AMPK Pathway

2020 ◽  
Vol 21 (24) ◽  
pp. 9617
Author(s):  
Eglantina Idrizaj ◽  
Rachele Garella ◽  
Silvia Nistri ◽  
Alfonso Dell’Accio ◽  
Emanuele Cassioli ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Multidisciplinary Approach ◽  
Gastric Fundus ◽  
Inhibitory Effects ◽  
Immunofluorescence Analysis ◽  
Synthesis Inhibitor ◽  
Ampk Signaling ◽  
Gastric Smooth Muscle ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach. The mechanical results showed that ADPN caused a decay of the strip basal tension, which was abolished by the nitric oxide (NO) synthesis inhibitor, L-NG-nitro arginine (L-NNA). The electrophysiological experiments confirmed that all ADPN effects were abolished by L-NNA, except for the reduction of Ca2+ current, which was instead prevented by the inhibitor of AMP-activated protein kinase (AMPK), dorsomorphin. The activation of the AMPK signaling by ADPN was confirmed by immunofluorescence analysis, which also revealed the ADPN R1 receptor (AdipoR1) expression in glial cells of the myenteric plexus. In conclusion, our results indicate that ADPN exerts an inhibitory action on the gastric smooth muscle by acting on AdipoR1 and involving the AMPK signaling pathway at the peripheral level. These findings provide novel bases for considering AMPK as a possible pharmacologic target for the potential treatment of obesity and eating disorders.

scholarly journals Inhibitory Effects of Dantrolene on Contractile Responses in Gastric Smooth Muscle of the Rat.

1994 ◽  
Vol 56 (2) ◽  
pp. 275-279 ◽  
Author(s):  
Kimihiko SATOH ◽  
Toshio OHTA ◽  
Shigeo ITO ◽  
Yoshikazu NAKAZATO
Keyword(s):  
Smooth Muscle ◽  
Inhibitory Effects ◽  
Contractile Responses ◽  
Gastric Smooth Muscle

Functional differences of Na+/Ca2+ exchanger expression in Ca2+ transport system of smooth muscle of guinea pig stomach

2005 ◽  
Vol 83 (8-9) ◽  
pp. 791-797 ◽  
Author(s):  
Yasushi Sakai ◽  
Hiroki Kinoshita ◽  
Keiichirou Saitou ◽  
Ikuo Homma ◽  
Koji Nobe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Guinea Pig ◽  
Gastric Fundus ◽  
Relaxation Cycle ◽  
Gastric Smooth Muscle ◽  
Guinea Pig Stomach ◽  
And Function ◽  
The Relationship ◽  
Ionophore Monensin

The plasma membrane ATP-dependent Ca2+ pump and the Na+/Ca2+ exchanger (NCX) are the major means of Ca2+ extrusion in smooth muscle. However, little is known regarding distribution and function of the NCX in guinea pig gastric smooth muscle. The expression pattern and distribution of NCX isoforms suggest a role as a regulator of Ca2+ transport in cells. Na+ pump inhibition and the consequent to removal of K+ caused gradual contraction in fundus. In contrast, the response was significantly less in antrum. Western blotting analysis revealed that NCX1 and NCX2 are the predominant NCX isoforms expressed in stomach, the former was expressed strongly in antrum, whereas the latter displayed greater expression in fundus. Isolated plasma membrane fractions derived from gastric fundus smooth muscle were also investigated to clarify the relationship between NCX protein expression and function. Na+-dependent Ca2+ uptake increased directly with Ca2+ concentration. Ca2+ uptake in Na+-loaded vesicles was markedly elevated in comparison with K+-loaded vesicles. Additionally, Ca2+ uptake by the Na+- or K+-loaded vesicles was substantially higher in the presence of A23187 than in its absence. The result can be explained based on the assumption that Na+ gradients facilitate downhill movement of Ca2+. Na+-dependent Ca2+ uptake was abolished by the monovalent cationic ionophore, monensin. NaCl enhanced Ca2+ efflux from vesicles, and this efflux was significantly inhibited by gramicidin. Results documented evidence that NCX2 isoform functionally contributes to Ca2+ extrusion and maintenance of contraction-relaxation cycle in gastric fundus smooth muscle.Key words: stomach, smooth muscle, Na+/Ca2+ exchanger (NCX), NCX2.

Influence of obestatin on the gastric longitudinal smooth muscle from mice: mechanical and electrophysiological studies

2013 ◽  
Vol 305 (9) ◽  
pp. G628-G637 ◽  
Author(s):  
Roberta Squecco ◽  
Rachele Garella ◽  
Fabio Francini ◽  
Maria Caterina Baccari
Keyword(s):  
Smooth Muscle ◽  
Membrane Conductance ◽  
Mechanical Activity ◽  
Synthesis Inhibitor ◽  
Specific Effects ◽  
Longitudinal Smooth Muscle ◽  
Gastric Smooth Muscle ◽  
Electrophysiological Studies ◽  
Peptide Precursor ◽  
Specific Membrane

Obestatin is a hormone released from the stomach deriving from the same peptide precursor as ghrelin. It is known to act as an anorectic hormone decreasing food intake, but contrasting results have been reported about the effects of obestatin on gastrointestinal motility. The aim of the present study was to investigate whether this peptide may act on the gastric longitudinal smooth muscle by using a combined mechanical and electrophysiological approach. When fundal strips from mice were mounted in organ baths for isometric recording of the mechanical activity, obestatin caused a tetrodotoxin-insensitive decrease of the basal tension and a reduction in amplitude of the neurally induced cholinergic contractile responses, even in the presence of the nitric oxide synthesis inhibitor NG-nitro-l-arginine. Obestatin reduced the amplitude of the response to the ganglionic stimulating agent dimethylphenyl piperazinium iodide but did not influence that to methacholine. In nonadrenergic, noncholinergic conditions, obestatin still decreased the basal tension of the preparations without influencing the neurally induced relaxant responses. For comparison, in circular fundal strips, obestatin had no effects. Notably, in the longitudinal antral ones, obestatin only caused a decrease of the basal tension. Electrophysiological experiments, performed by a single microelectrode inserted in a gastric longitudinal smooth muscle cell, showed that obestatin had similar effects in fundal and antral preparations: it decreased the resting specific membrane conductance, inhibited Ca2+ currents, and positively shifted their voltage threshold of activation. In conclusion, the present results indicate that obestatin influences gastric smooth muscle exerting site-specific effects.

scholarly journals Mechanism of AMPK-mediated apoptosis of rat gastric smooth muscle cells under high glucose condition

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Xiang-zi Zhang ◽  
Mo-han Zhang ◽  
Xue-sen Fang ◽  
Xiang-shu Cui ◽  
Zheng Jin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
High Glucose ◽  
Muscle Cells ◽  
Ampk Signaling ◽  
Gastric Smooth Muscle ◽  
High Glucose Condition ◽  
Ampk Activity ◽  
Glucose Condition

Abstract To observe changes in AMP-activated protein kinase (AMPK) activity and phosphorylation changes in AMPK signaling pathway in gastric smooth muscle cells of rats with diabetic gastroparesis (DGP), investigate the effect of AMPK on apoptosis and explore the underlying mechanism. After establishing rat model of DGP, rats were divided into normal control (NC) and DGP groups. The phosphorylation changes in AMPK pathway were detected by AMPK Signaling Phospho-Antibody Array, and the apoptosis-related proteins were determined. Rat gastric smooth muscle cells were cultured in vitro under different glucose conditions, and divided into normal and high glucose groups. The AMPK activity and intracellular Ca2+ changes in cells were observed. After AMPK silencing, cells were divided into high glucose-24h, high glucose-48h and high glucose-48h+siRNA groups. Changes in expression of apoptosis-related proteins were observed. AMPK activity and apoptosis rates were both increased in gastric smooth muscle tissues in DGP rats (P<0.05, P<0.001, respectively). A total of 14 apoptosis-related differentially phosphorylated proteins were identified. Under high-glucose condition, AMPK activity and intracellular Ca2+ concentrations in rat gastric smooth muscle cells were increased (both P<0.05). After AMPK silencing, p53 expression was decreased, Akt and p70 S6 ribosomal protein kinase (p70S6K) activities were were increased, Bcl-2 expression was increased, CaMKII activity was decreased in the high glucose-48h group. Under high-glucose condition, activated AMPK can directly or indirectly promote cells apoptosis by regulating the expression and activity of p53, Akt, p70S6K, Protein kinase A (PKA), Phospholipidol C (PLC)-β3, CaMKII, CaMKIV and eukaryotic translation initiation factor 4E binding protein1 (4E-BP1) in rat gastric smooth muscle cells.

scholarly journals Inhibition of RhoA-dependent pathway and contraction by endogenous hydrogen sulfide in rabbit gastric smooth muscle cells

2015 ◽  
Vol 308 (6) ◽  
pp. C485-C495 ◽  
Author(s):  
Ancy D. Nalli ◽  
Senthilkumar Rajagopal ◽  
Sunila Mahavadi ◽  
John R. Grider ◽  
Karnam S. Murthy
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Contraction ◽  
Light Chain ◽  
Rho Kinase ◽  
Muscle Cells ◽  
Inhibitory Effects ◽  
Gastric Smooth Muscle ◽  
Camp And Cgmp ◽  
Cgmp Formation

Inhibitory neurotransmitters, chiefly nitric oxide and vasoactive intestinal peptide, increase cyclic nucleotide levels and inhibit muscle contraction via inhibition of myosin light chain (MLC) kinase and activation of MLC phosphatase (MLCP). H2S produced as an endogenous signaling molecule synthesized mainly from l-cysteine via cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS) regulates muscle contraction. The aim of this study was to analyze the expression of CSE and H2S function in the regulation of MLCP activity, 20-kDa regulatory light chain of myosin II (MLC20) phosphorylation, and contraction in isolated gastric smooth muscle cells. Both mRNA expression and protein expression of CSE, but not CBS, were detected in smooth muscle cells of rabbit, human, and mouse stomach. l-cysteine, an activator of CSE, and NaHS, a donor of H2S, inhibited carbachol-induced Rho kinase and PKC activity, Rho kinase-sensitive phosphorylation of MYPT1, PKC-sensitive phosphorylation of CPI-17, and MLC20 phosphorylation and sustained muscle contraction. The inhibitory effects of l-cysteine, but not NaHS, were blocked upon suppression of CSE expression by siRNA or inhibition of its activity by dl-propargylglycine (PPG) suggesting that the effect of l-cysteine is mediated via activation of CSE. Glibenclamide, an inhibitor of KATP channels, had no effect on the inhibition of contraction by H2S. Both l-cysteine and NaHS had no effect on basal cAMP and cGMP levels but augmented forskolin-induced cAMP and SNP-induced cGMP formation. We conclude that both endogenous and exogenous H2S inhibit muscle contraction, and the mechanism involves inhibition of Rho kinase and PKC activities and stimulation of MLCP activity leading to MLC20 dephosphorylation and inhibition of muscle contraction.

Identification of neurotransmitters by selective protection of postjunctional receptors

1990 ◽  
Vol 258 (1) ◽  
pp. G103-G106
Author(s):  
J. R. Grider
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Gastric Fundus ◽  
Membrane Receptors ◽  
Field Stimulation ◽  
Dibutyryl Camp ◽  
Selective Protection ◽  
Gastric Smooth Muscle ◽  
Selective Ligands ◽  
Before And After

The neurotransmitter responsible for relaxation of gastric smooth muscle was identified by a technique involving the use of selective ligands to protect postjunctional receptors combined with inactivation of all other receptors with N-ethylmaleimide (NEM). Relaxation in response to field stimulation (80 V, 1 ms, 0.5-8 Hz) and to maximally effective concentrations of vasoactive intestinal peptide (VIP; 1 microM), ATP (1 mM), isoproterenol (1 mM), dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP; 1 mM), and forskolin (1 microM) was measured in muscle strips from guinea pig gastric fundus before and after treatment with NEM (5 microM) for 1 h. Protection of VIP receptors with VIP or the VIP antagonist VIP10-28 fully protected relaxation induced by VIP and by field stimulation, but did not protect relaxation induced by ATP or isoproterenol. Protection of ATP receptors with ATP protected only the response to ATP, but did not protect the response to field stimulation, VIP, or isoproterenol. Relaxation induced by either forskolin or dibutyryl cAMP was not altered by treatment with NEM alone or in the presence of protective ligands, indicating that at the concentrations used NEM inactivated membrane receptors without affecting intracellular relaxation mechanisms. These studies indicate that VIP but not ATP is the neurotransmitter responsible for neurally induced relaxation in the gastric fundus.

Comparative Study of pA2 Values of Pirenzepine and Atropine for Guinea-Pig Gastric Fundus and Gastric Smooth Muscle

Pharmacology ◽  
1984 ◽  
Vol 29 (6) ◽  
pp. 329-335 ◽  
Author(s):  
Del Tacca ◽  
G. Soldani ◽  
C. Bernardini ◽  
E. Martinotti
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Comparative Study ◽  
Gastric Fundus ◽  
Gastric Smooth Muscle

Contractile effects of female reproductive hormones on gastric smooth muscle

2001 ◽  
Vol 120 (5) ◽  
pp. A463-A463
Author(s):  
A JAMES ◽  
J RYAN ◽  
H PARKMAN
Keyword(s):  
Smooth Muscle ◽  
Reproductive Hormones ◽  
Gastric Smooth Muscle
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