MAPK mediates PKC-dependent contraction of cat esophageal and lower esophageal sphincter circular smooth muscle

2003 ◽  
Vol 285 (1) ◽  
pp. G86-G95 ◽  
Author(s):  
Weibiao Cao ◽  
Uy Dong Sohn ◽  
Khalil N. Bitar ◽  
Jose Behar ◽  
Piero Biancani ◽  
...  
Keyword(s):  
Lower Esophageal Sphincter ◽  
P38 Mapk ◽  
Kinase Inhibitor ◽  
Circular Muscle ◽  
Circular Smooth Muscle ◽  
Mapk Activity ◽  
Esophageal Sphincter ◽  
P38 Mapk Inhibitor ◽  
Sb 203580 ◽  
Mapk Inhibitor

Esophageal (ESO) circular muscle contraction and lower esophageal sphincter (LES) tone are PKC dependent. Because MAPKs may be involved in PKC-dependent contraction, we examined ERK1/ERK2 and p38 MAPKs in ESO and LES. In permeabilized LES muscle cells, ERK1/2 antibodies reduced 1,2-dioctanoylglycerol (DG)- and threshold ACh-induced contraction, which are PKC dependent, but not maximal ACh, which is calmodulin dependent. LES tone was reduced by the ERK1/2 kinase inhibitor PD-98059 and by the p38 MAPK inhibitor SB-203580. In permeable ESO cells, ACh contraction was reduced by ERK1/ERK2 and p38 MAPK antibodies and by PD-98059 and SB-203580. ACh increased MAPK activity and phosphorylation of MAPK and of p38 MAPK. The 27-kDa heat shock protein (HSP27) antibodies reduced ACh contraction. HSP27 and p38 MAPK antibodies together caused no greater inhibition than either one alone. p38 MAPK and HSP27 coprecipitated after ACh stimulation, suggesting that HSP27 is linked to p38 MAPK. These data suggest that PKC-dependent contraction in ESO and LES is mediated by the following two distinct MAPK pathways: ERK1/2 and HSP27-linked p38 MAPK.

IL-1β signaling in cat lower esophageal sphincter circular muscle

2006 ◽  
Vol 291 (4) ◽  
pp. G672-G680 ◽  
Author(s):  
Weibiao Cao ◽  
Ling Cheng ◽  
Jose Behar ◽  
Piero Biancani ◽  
Karen M. Harnett
Keyword(s):  
Lower Esophageal Sphincter ◽  
P38 Mapk ◽  
Circular Muscle ◽  
Circular Smooth Muscle ◽  
Sequential Activation ◽  
Cox 2 ◽  
Esophageal Sphincter ◽  
Sb 203580

In a cat model of acute experimental esophagitis, resting in vivo lower esophageal sphincter (LES) pressure and in vitro tone are lower than in normal LES, and the LES circular smooth muscle layer contains elevated levels of IL-1β that decrease the LES tone of normal cats. We now examined the mechanisms of IL-1β-induced reduction in LES tone. IL-1β significantly reduced acetylcholine-induced Ca2+ release in Ca2+-free medium, and this effect was partially reversed by catalase, demonstrating a role of H2O2 in these changes. IL-1β significantly increased the production of H2O2, and the increase was blocked by the p38 MAPK inhibitor SB-203580, by the cytosolic phospholipase A2 (cPLA2) inhibitor AACOCF3, and by the NADPH oxidase inhibitor apocynin, but not by the MEK1 inhibitor PD-98059. IL-1β significantly increased the phosphorylation of p38 MAPK and cPLA2. IL-1β-induced cPLA2 phosphorylation was blocked by SB-203580 but not by AACOCF3, suggesting sequential activation of p38 MAPK-phosphorylating cPLA2. The IL-1β-induced reduction in LES tone was partially reversed by AACOCF3 and by the Ca2+-insensitive PLA2 inhibitor bromoenol lactone (BEL). IL-1β significantly increased cyclooxygenase (COX)-2 and PGE2 levels. The increase in PGE2 was blocked by SB-203580, AACOCF3, BEL, and the COX-2 inhibitor NS-398 but not by PD-98059 or the COX-1 inhibitor valeryl salicylate. The data suggested that IL-1β reduces LES tone by producing H2O2, which may affect Ca2+-release mechanisms and increase the synthesis of COX-2 and PGE2. Both H2O2 and PGE2 production depend on sequential activation of p38 MAPK and cPLA2. cPLA2 activates NADPH oxidases, producing H2O2, and may produce arachidonic acid, converted to PGE2 via COX-2.

Inhibition of lower esophageal sphincter circular muscle by female sex hormones.

1978 ◽  
Vol 234 (3) ◽  
pp. E243 ◽  
Author(s):  
R S Fisher ◽  
G S Roberts ◽  
C J Grabowski ◽  
S Cohen
Keyword(s):  
Lower Esophageal Sphincter ◽  
Sex Hormones ◽  
Circular Muscle ◽  
Response Curves ◽  
Circular Smooth Muscle ◽  
Female Sex ◽  
Female Sex Hormones ◽  
Esophageal Sphincter ◽  
Muscle Responses

To determine the effect of estrogenic and progesteronic activity on lower esophageal sphincter (LES) circular muscle, studies were performed on 20 adult opossums. Does-response curves on circular smooth muscle strips from the LES were constructed for gastrin and acetylcholine alone, and with 17beta-estradiol and/or progesterone added. Each female hormone significantly decreased the maximal LES muscle responses to gastrin and acetylcholine. A combination of 17beta-estradiol and progesterone abolished the response to gastrin. In contrast, the male sex hormone, dihydrotestosterone, had no effect. In conclusion, administration of estrogen and progesteron, but not dihydrotestosterone, in vitro reduced LES muscle responses to gastrin and acetylcholine. These studies suggest that the female sex hormones can alter LES function and potentially may be of importance in the pathogenesis of heartburn of pregnancy.

VIP-induced alterations in cAMP and inositol phosphates in the lower esophageal sphincter

1990 ◽  
Vol 259 (2) ◽  
pp. G239-G244 ◽  
Author(s):  
S. M. Szewczak ◽  
J. Behar ◽  
G. Billett ◽  
C. Hillemeier ◽  
B. Y. Rhim ◽  
...  
Keyword(s):  
Lower Esophageal Sphincter ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Circular Muscle ◽  
Tissue Samples ◽  
Cyclic Monophosphate ◽  
Circular Smooth Muscle ◽  
Esophageal Sphincter ◽  
Camp Levels

Adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and inositol phosphate (IP) levels were measured in thin tissue samples from the circular smooth muscle of the cat lower esophageal sphincter (LES) at 37 degrees C during vasoactive intestinal peptide (VIP)-induced relaxation. On exposure of in vitro LES circular muscle strips to 10(-6) M VIP at the same temperature, relaxation of spontaneous resting tone begins within 3-6 s, is half maximal at 30 s, and maximal at 1 min. VIP-induced changes in cAMP, cGMP, and IP metabolite levels were measured at 5 and 30 s after the addition of 10(-6) M VIP. At 5 s cAMP levels increased significantly with respect to time-matched unstimulated controls, whereas inositol 1,4,5-trisphosphate (1,4,5-IP3) decreased and these changes remained constant at 30 s. cGMP levels were unchanged at either 5 or 30 s after exposure to 10(-6) M VIP. These data suggest that VIP-induced relaxation is temporally linked to decreased 1,4,5-IP3 as well as increased cAMP levels.

scholarly journals The Proto-oncoprotein Brx Activates Estrogen Receptor β by a p38 Mitogen-activated Protein Kinase Pathway

2001 ◽  
Vol 276 (50) ◽  
pp. 46792-46797 ◽  
Author(s):  
Paul H. Driggers ◽  
James H. Segars ◽  
Domenica M. Rubino
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Active Form ◽  
Mitogen Activated Protein Kinase ◽  
The Novel ◽  
Mapk Activity ◽  
Dependent Activity ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor

The estrogen receptors (ERs) are ligand-inducible transcription factors that play key roles in the control of growth and differentiation in reproductive tissues. We showed that the novel Dbl family proto-oncoprotein Brx enhances ligand-dependent activity of ERα via a Cdc42-dependent pathway. Brx also significantly enhances ligand-dependent activity of ERβ. This enhancement is not affected by inhibition of p44/42 mitogen-activated protein kinase (MAPK) activation by PD98059. However, addition of the p38 MAPK inhibitor SB202190 abrogates the enhancement of ERβ activity by Brx, showing that p38 MAPK activity is required for the enhancement of ERβ function by Brx. In COS-7 cells, transfection of Brx leads to activation of endogenous p38 MAPK activity. Co-expression of the β2 isoform of human p38 MAPK and a constitutively active form of the p38 MAPK kinase MKK6 (MKK6-EE) synergistically augments ligand-dependent activity of ERβ. Our findings suggest that p38 MAPKs may be important regulators of ERβ activity.

448 CARDIOPROTECTIVE EFFECT OF A COMBINATION OF RHO-KINASE INHIBITOR AND P38 MAPK INHIBITOR ON CARDIOVASCULAR REMODELING IN DAHL RATS

2012 ◽  
Vol 30 ◽  
pp. e132-e133
Author(s):  
Mayuko Ishikawa ◽  
Naohiko Kobayashi ◽  
Hiroshi Takeshima ◽  
Wataru Koguchi ◽  
Fumihiro Sugiyama ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Cardioprotective Effect ◽  
Cardiovascular Remodeling ◽  
Rho Kinase Inhibitor ◽  
P38 Mapk Inhibitor ◽  
Mapk Inhibitor
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