scholarly journals Effect of 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones on the bradykinin-induced smooth muscle contraction

2017 ◽  
Vol 8 (1) ◽  
pp. 30-35
Author(s):  
P. A. Virych ◽  
O. V. Shelyuk ◽  
T. A. Kabanova ◽  
O. I. Khalimova ◽  
V. S. Martynyuk ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Competitive Inhibitor ◽  
Smooth Muscle Contraction ◽  
Signal Transduction Pathways ◽  
Channel Blockers ◽  
Normal Functioning ◽  
Inhibitory Interaction ◽  
Additional Reduction

Damage to tissue, inflammation and disruption of normal functioning of organs are often accompanied by pain. In pain perceptions, the kinin-kallikrein system with bradykinin as mediator is very important. Regulatory activity of the kinin-kallikrein system permits the control of inflammation, pain, vascular tone and other functions. A new group of substances that may used for this purpose are 3-substituted 1,4-benzdiazepinones. We analyzed the effect of 3-aryl amino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones derivatives on the normalized maximal rate of bradykinin-induced smooth muscle contraction of the stomach in the presence of calcium channel blockers verapamil (1 μM) and gadolinium (300 μM). The levels of bradykinin and 3-arylamino-1,2-dihydro-3H-1,4-benzodiazepine-2-ones in the incubation solution were 10–6 M. Data processing on the dynamics of contraction was performed according to the method of T. Burdyha and S. Kosterin. Statistically significant changes were found for MX-1828. This compound reduced the maximal normalized rate of bradykinin-induced smooth muscle contraction in the presence of Gd3+ and verapamil by 19.3% and 32.0%, respectively. Also, MX-1828 demonstrated effects similar to those of the competitive inhibitor bradykinin B2-receptor – des-Arg9-bradykinin-acetate, which is possible evidence of its interaction with the receptor or signal transduction pathways. MX-1828 additionally reduced the maximum normalized rate of relaxation by 6.2% in the presence of Gd3+. This effect was demonstrated for MX-1906 in the presence of verapamil with additional reduction of the maximal normalized rate of relaxation, which was 26.4%. The results suggest the presence of inhibitory interaction between MX-1828 and kinin-kallikrein system receptors or signal transduction pathways. The effects which were found for MX-1906 require further studies to clarify the mechanisms of influence on bradykinin-induced smooth muscle contraction.

Signal Transduction Pathways Mediating CCK-8S-Induced Gastric Antral Smooth Muscle Contraction

Digestion ◽  
2006 ◽  
Vol 73 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Xin-Min Si ◽  
Lei Huang ◽  
Shelley Chireyath Paul ◽  
Ping An ◽  
He-Sheng Luo
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Signal Transduction Pathways

HSP27 in signal transduction and association with contractile proteins in smooth muscle cells

1999 ◽  
Vol 277 (2) ◽  
pp. G445-G454 ◽  
Author(s):  
Adenike I. Ibitayo ◽  
Jeanette Sladick ◽  
Sony Tuteja ◽  
Otto Louis-Jacques ◽  
Hirotaka Yamada ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Contractile Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Cascade ◽  
Kinase C ◽  
Mitogen Activated Protein

Sustained smooth muscle contraction is mediated by protein kinase C (PKC) through a signal transduction cascade leading to contraction. Heat-shock protein 27 (HSP27) appears to be the link between these two major events, i.e., signal transduction and sustained smooth muscle contraction. We have investigated the involvement of HSP27 in signal transduction and HSP27 association with contractile proteins (e.g., actin, myosin, tropomyosin, and caldesmon) resulting in sustained smooth muscle contraction. We have carried out confocal microscopy to investigate the cellular reorganization and colocalization of proteins and immunoprecipitation of HSP27 with actin, myosin, tropomyosin, and caldesmon as detected by sequential immunoblotting. Our results indicate that 1) translocation of Raf-1 to the membrane when stimulated with ceramide is inhibited by vasoactive intestinal peptide (VIP), a relaxant neuropeptide; 2) PKC-α and mitogen-activated protein kinase translocate and colocalize on the membrane in response to ceramide, and PKC-α translocation is inhibited by VIP; 3) HSP27 colocalizes with actin when contraction occurs; and 4) HSP27 immunoprecipitates with actin and with the contractile proteins myosin, tropomyosin, and caldesmon. We propose a model in which HSP27 is involved in sustained smooth muscle contraction and modulates the interaction of actin, myosin, tropomyosin, and caldesmon.

scholarly journals A Review of Signal Transduction in Mechanisms of Smooth Muscle Contraction and Its Relevance for Specialized Physical Therapy

2013 ◽  
Vol 25 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Ju-Hyun Kim ◽  
Lim-Kyu Lee ◽  
Won-Deok Lee ◽  
Jeong-Uk Lee ◽  
Mee-Young Kim ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Physical Therapy ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction

Ca2+ antagonist-insensitive coronary smooth muscle contraction involves activation of ϵ-protein kinase C-dependent pathway

2003 ◽  
Vol 285 (6) ◽  
pp. C1454-C1463 ◽  
Author(s):  
Andrea Dallas ◽  
Raouf A. Khalil
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Muscle Contraction ◽  
Smooth Muscle Contraction ◽  
Channel Blockers ◽  
Cell Contraction ◽  
Coronary Smooth Muscle ◽  
Calphostin C ◽  
Gf 109203X ◽  
Dependent Pathway

Certain angina and coronary artery disease forms do not respond to Ca2+ channel blockers, and a role for vasoactive eicosanoids such as PGF2α in Ca2+ antagonist-insensitive coronary vasospasm is suggested; however, the signaling mechanisms are unclear. We investigated whether PGF2α-induced coronary smooth muscle contraction is Ca2+ antagonist insensitive and involves activation of a PKC-dependent pathway. We measured contraction in single porcine coronary artery smooth muscle cells and intracellular free Ca2+ concentration ([Ca2+]i) in fura 2-loaded cells and examined cytosolic and particulate fractions for PKC activity and reactivity with isoform-specific PKC antibodies. In Hanks' solution (1 mM Ca2+), PGF2α (10-5 M) caused transient [Ca2+]i increase followed by maintained [Ca2+]i increase and 34% cell contraction. Ca2+ channel blockers verapamil and diltiazem (10-6 M) abolished maintained PGF2α-induced [Ca2+]i increase but only partially inhibited PGF2α-induced cell contraction to 17%. Verapamil-insensitive PGF2α contraction was inhibited by PKC inhibitors GF-109203X, calphostin C, and ϵ-PKC V1-2. PGF2α caused Ca2+-dependent α-PKC and Ca2+-independent ϵ-PKC translocation from cytosolic to particulate fractions that was inhibited by calphostin C. Verapamil abolished PGF2α-induced α-but not ϵ-PKC translocation. PMA (10-6 M), a direct activator of PKC, caused 21% contraction with no significant [Ca2+]i increase and ϵ-PKC translocation that were inhibited by calphostin C but not verapamil. Membrane depolarization by 51 mM KCl, which stimulates Ca2+ influx, caused 36% cell contraction and [Ca2+]i increase that were inhibited by verapamil but not GF-109203X or calphostin C and did not cause α- or ϵ-PKC translocation. Thus a significant component of PGF2α-induced contraction of coronary smooth muscle is Ca2+ antagonist insensitive, involves Ca2+-independent ϵ-PKC activation and translocation, and may represent a signaling mechanism of Ca2+ antagonist-resistant coronary vasospasm.

scholarly journals Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

2016 ◽  
Vol 21 (2) ◽  
pp. 19-23
Author(s):  
P. Virych ◽  
O. Shelyuk ◽  
V. Martynyuk ◽  
V. Pavlovsky
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Competitive Inhibitor ◽  
Smooth Muscle Contraction ◽  
Gastric Smooth Muscle ◽  
Low Concentrations

The effect of compounds based on 3-substituted-1,4-benzodiazepine-2-ones on contractile activity of smooth muscles of the rat's stomach was analyzed. Action substances MX-1626, MX-1775 for the smooth muscle contraction of like competitive inhibitor of bradykinin – des-Arg9- [Leu8]-Bradykinin acetate, which is observed as increase normalized rate of contraction with increasing of bradykinin concentration and characterized by a slowdown in the first phase of contraction. The most effective 3-subtituted 1,4-benzodiazepin-2-ones was at low concentrations of bradykinin, increasing it concentration their effect is reduced.

Interactions of oxidant stress and vascular reactivity

1991 ◽  
Vol 260 (4) ◽  
pp. L207-L211 ◽  
Author(s):  
G. H. Gurtner ◽  
T. Burke-Wolin
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Guanylate Cyclase ◽  
Physiological Response ◽  
Vascular Reactivity ◽  
Oxidant Stress ◽  
Smooth Muscle Contraction

Oxidants have complex effects on pulmonary vascular reactivity. They can stimulate production of vasoconstrictor arachidonate mediators and can also cause vasodilation through activation of guanylate cyclase. Oxidants can also inactivate vasomotor phenomenon by interfering with mechanisms of signal transduction or smooth muscle contraction. The final physiological response depends on the balance of these complex actions.

Myosin phosphorylation/dephosphorylation and regulation of airway smooth muscle contractility

1991 ◽  
Vol 261 (2) ◽  
pp. L1-L14 ◽  
Author(s):  
P. de Lanerolle ◽  
R. J. Paul
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Protein Kinases ◽  
Airway Smooth Muscle ◽  
Smooth Muscles ◽  
Smooth Muscle Contraction ◽  
Energy Transduction ◽  
Signal Integration ◽  
Myosin Phosphorylation

Airway smooth muscles contract due to the activation of a highly sophisticated signal transduction mechanism. Signal transduction in muscle must include 1) a mechanism for converting chemical energy (i.e., ATP) into mechanical work (energy transduction) and 2) a mechanism for integrating the response to multiple stimuli (signal integration). In smooth and striated muscles, ATP hydrolysis due to the cyclic interaction of actin and myosin is the final site for both energy transduction and signal integration. There is growing consensus that this interaction in smooth muscles is regulated by the phosphorylation/dephosphorylation of the 20-kDa light chain of smooth muscle myosin. By phosphorylation/dephosphorylation we mean the enzyme-catalyzed transfer of the terminal phosphate of ATP to a serine or threonine residue on a protein, by a class of enzymes known as protein kinases, with the formation of a covalent phosphoester linkage and the enzyme-catalyzed removal of the phosphate group by phosphoprotein phosphatases. Smooth muscles contain many protein kinases and phosphatases, and the research emphasis on the regulation of smooth muscle contraction has focused on how these enzymes act individually and in concert to regulate the actin-myosin interaction. This review will describe the biochemical and physiological experiments that have been performed to understand the role of myosin phosphorylation/dephosphorylation in regulating smooth muscle contraction. Although data from studies on vascular and other smooth muscles will be summarized, this review will focus on studies performed on airway smooth muscle. More detailed reviews of studies on nonairway smooth muscles can be found in Refs. 47 and 79.

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