Group I secreted PLA2and arachidonic acid metabolites in the maintenance of cat LES tone

1999 ◽  
Vol 277 (3) ◽  
pp. G585-G598 ◽  
Author(s):  
W. B. Cao ◽  
K. M. Harnett ◽  
Q. Chen ◽  
M. K. Jain ◽  
J. Behar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
G Proteins ◽  
Circular Muscle ◽  
Group I ◽  
Gtpγs Binding ◽  
Acid Metabolites ◽  
Esophageal Sphincter

Spontaneous tone of in vitro lower esophageal sphincter (LES) circular muscle is associated with elevated levels of arachidonic acid (AA), PGF2α, and increased [35S]guanosine 5′- O-(3-thiotriphosphate) (GTPγS) binding to Gq-, Gi3-, and Gi1/i2-like G proteins. Tone and AA levels were reduced by inhibitors of a pancreatic-like (group I) secreted phospholipase A2(sPLA2), by the cyclooxygenase inhibitor indomethacin, and by the thromboxane A2antagonist SQ-29548. In addition, pertussis toxin (PTX) reduced LES tone, confirming a role of PTX-sensitive G proteins in maintenance of LES tone. PGF2αcontracted LES smooth muscle (strips and cells) and increased [35S]GTPγS binding to Gqand Gi3in solubilized LES circular muscle membranes. PGF2α-induced contraction of LES permeable muscle cells was inhibited by Gqand Gi3but not by Gi1/i2and Goantibodies. The thromboxane A2analog U-46619 contracted LES smooth muscle and increased Gqbinding. U-46619-induced contraction was inhibited by Gqbut not by Gi3, Gi1/i2, and Goantibodies. LES tone and [35S]GTPγS binding were significantly reduced by indomethacin. We conclude that group I sPLA2may mediate “spontaneous” LES tone by producing AA, which is metabolized to PGF2αand thromboxane A2. These AA metabolites activate receptors linked to Gi3and Gqto maintain LES contraction.

Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle

2005 ◽  
Vol 288 (4) ◽  
pp. G787-G797 ◽  
Author(s):  
Ling Cheng ◽  
Weibiao Cao ◽  
Jose Behar ◽  
Piero Biancani ◽  
Karen M. Harnett
Keyword(s):  
Arachidonic Acid ◽  
Circular Muscle ◽  
Arachidonic Acid Metabolism ◽  
Acid Metabolites ◽  
Esophageal Sphincter ◽  
Cat Model ◽  
Induced Changes

Myogenic lower esophageal sphincter (LES) tone is maintained by arachidonic acid metabolites, such as PGF2α and thromboxane A2/B2. Experimental esophagitis in cat reduces LES in vivo pressure and in vitro tone. Because IL-1β may mediate esophagitis-associated reduction in ACh release in esophagus, we examined whether IL-1β may also play a role in esophagitis-induced reduction of LES tone. A cat model of experimental esophagitis was obtained by repeated esophageal perfusion with HCl (Biancani P, Barwick K, Selling J, and McCallum R. Gastreonterology 87: 8–16, 1984 and Sohn UD, Harnett KM, Cao W, Rich H, Kim N, Behar J, and Biancani P. J Pharmacol Exp Ther 283: 1293–1304, 1997.). LES circular muscle strips were examined in muscle chambers as previously described (Biancani P, Billett G, Hillemeier C, Nissenshon M, Rhim BY, Sweczack S, and Behar J. Gastroenterology 103: 1199–1206, 1992). Levels of inflammatory mediators were measured. IL-1β levels were higher in esophagitis than in normal LES. IL-1β reduced normal LES tone, and the reduction was reversed by catalase, suggesting a role of H2O2. This was confirmed by IL-1β-induced production of H2O2 in normal LES and elevated H2O2 levels in esophagitis. H2O2 by itself is sufficient to explain the changes that occur in the muscle, reducing its ability to contract. H2O2 increased PGE2 in normal LES, and PGE2 levels were elevated in esophagitis LES, whereas PGF2α levels were unchanged. H2O2 also increased levels of 8-isoprostanes, stable prostaglandin-like compounds formed by free radical-induced peroxidation of arachidonic acid, and 8-isoprostane levels were elevated in esophagitis. The PGF2α analog 8-iso-PGF2α caused little contraction of LES strips but reduced PGF2α binding and contraction of normal LES. In esophagitis, PGF2α binding and contraction were reduced in LES, suggesting that isoprostanes may contribute to reduction in tone in esophagitis. The data suggest that, in esophagitis, IL-1β causes production of H2O2. H2O2 increases PGE2, which relaxes the LES, and 8-iso-F2α, which blocks PGF2α-mediated contraction.

The role of novel arachidonic acid metabolites in GnRH action on gonadotropin release in vitro.

1987 ◽  
Vol 116 (3_Suppl) ◽  
pp. S153
Author(s):  
L. KIESEL ◽  
A. PRZYLIPIAK ◽  
I. EBERHARDT ◽  
B. RUNNEBAUM
Keyword(s):  
Arachidonic Acid ◽  
Gonadotropin Release ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites ◽  
Release In Vitro

scholarly journals Downregulation of Gαq-11protein expression in guinea pig antral and colonic circular muscle during pregnancy

1999 ◽  
Vol 276 (4) ◽  
pp. G895-G900 ◽  
Author(s):  
Qian Chen ◽  
Zuo-Liang Xiao ◽  
Piero Biancani ◽  
Jose Behar
Keyword(s):  
Smooth Muscle ◽  
G Proteins ◽  
Guinea Pigs ◽  
Muscle Relaxation ◽  
Circular Muscle ◽  
Enzymatic Digestion ◽  
Inhibitory Effect ◽  
Smooth Muscle Contractility ◽  
Circular Smooth Muscle ◽  
Gtpγs Binding

Pregnancy has an inhibitory effect on motility of the gastrointestinal tract. The present study was designed to examine the mechanisms responsible for antral and colonic hypomotility in pregnant guinea pigs. Circular smooth muscle cells from the antrum and left colon were isolated by enzymatic digestion with collagenase from pregnant and nonpregnant guinea pigs. Contractile responses to agonists were expressed as percent shortening from resting cell length. The function of G proteins in antral and colonic circular smooth muscle was assessed by [35S]guanosine 5′- O-(3-thiotriphosphate) (GTPγS) binding induced by CCK-8 and G protein quantitation. The contraction of antral and colonic circular smooth muscle from pregnant guinea pigs was reduced in response to CCK-8 and to GTPγS but was normal in response to KCl andd- myo-inositol 1,4,5-trisphosphate compared with nonpregnant animals. The stimulation of [35S]GTPγS binding to Gαq-11induced by 1 μM CCK-8 was significantly lower in antral and colonic circular smooth muscle from pregnant guinea pigs than that in controls. Furthermore, Western blot analysis showed a decreased Gαq-11and an increased Gsα protein content in both tissues during pregnancy. It is concluded that pregnancy appears to impair gastrointestinal circular smooth muscle contractility by downregulating G proteins such as Gαq-11protein, which mediates muscle contraction, and upregulating Gsα protein, which mediates muscle relaxation.

VIP and acetylcholine: neurotransmitters in esophageal circular smooth muscle

1989 ◽  
Vol 257 (3) ◽  
pp. G380-G385 ◽  
Author(s):  
J. Behar ◽  
V. Guenard ◽  
J. H. Walsh ◽  
P. Biancani
Keyword(s):  
Smooth Muscle ◽  
Electrical Stimulation ◽  
Sodium Nitroprusside ◽  
Vasoactive Intestinal Polypeptide ◽  
Circular Muscle ◽  
Circular Smooth Muscle ◽  
Excitatory Neurotransmitters ◽  
Esophageal Sphincter ◽  
Dose Dependent

Vasoactive intestinal polypeptide (VIP) and acetylcholine were evaluated as possible inhibitory and excitatory neurotransmitters in the cat esophageal circular smooth muscle. Circular muscle strips 2 mm in thickness were obtained from 1 to 3.4 cm above the lower esophageal sphincter and tested in vitro. Muscle strips contracted with bethanechol (10(-5) M) were relaxed by electrical stimulation (0.5-5 Hz) and by VIP (10(-8)-10(-6) M). Relaxation induced by electrical stimulation was blocked by tetrodotoxin, whereas VIP-induced relaxation was not affected. Highly specific VIP antiserum (5%) antagonized both VIP and electrically induced relaxation, and the antagonism was eliminated when the antiserum was neutralized with VIP (10(-6.5) M). Dopamine (10(-4) M) reduced the relaxation induced both by exogenous VIP and by electrical stimulation but did not affect the relaxation caused by sodium nitroprusside (10(-8)-10(-5) M). In untreated strips, physostigmine (10(-10)-10(-8) M) enhanced the off contraction in response to electrical stimulation, whereas atropine caused a dose-dependent reduction with complete abolition at 10(-4) M. These data suggest that in the esophagus inhibition and excitation are mediated by distinct mechanisms: VIP mediates inhibition and acetylcholine is responsible for the off contraction in response to electrical stimulation.

Role of 100-kDa cytosolic PLA2 in ACh-induced contraction of cat esophageal circular muscle

1994 ◽  
Vol 267 (3) ◽  
pp. G433-G441 ◽  
Author(s):  
U. D. Sohn ◽  
D. K. Kim ◽  
J. V. Bonventre ◽  
J. Behar ◽  
P. Biancani
Keyword(s):  
Arachidonic Acid ◽  
Circular Muscle ◽  
Nordihydroguaiaretic Acid ◽  
Kinase C ◽  
Acid Release ◽  
Esophageal Sphincter ◽  
Cytosolic Pla2 ◽  
Dependent Pathway ◽  
Esophageal Contraction

We have shown that acetylcholine (ACh)-induced contraction of esophageal circular muscle cells is mediated by activation of protein kinase C (PKC). We now examine the role of phospholipase A2 (PLA2). ACh increases [3H]arachidonic acid release in esophageal but not in lower esophageal sphincter (LES) muscle. In addition, ACh-induced contraction of esophageal but not of LES cells was reduced by the PLA2 antagonist dimethyleicosadienoic acid and by antiserum to a 100-kDa cytosolic PLA2 (cPLA2). These data suggest that the 100-kDa cPLA2 plays a role in ACh-induced contraction of esophageal but not of LES muscle. In esophageal cells, arachidonic acid produced by PLA2 caused little contraction by itself but potentiated contraction induced by the PKC agonist diacylglycerol (DAG). The free fatty acids linoleic acid and linolenic acid also potentiated DAG-induced contraction. Indomethacin and nordihydroguaiaretic acid had no effect on arachidonic acid-induced potentiation of DAG. The potentiation of DAG-induced contraction by arachidonic acid was inhibited by the PKC inhibitor H-7, but it was not affected by the calmodulin inhibitor CGS-9343B. We conclude that a 100-kDa cPLA2 participates in ACh-induced esophageal contraction by producing arachidonic acid and potentiating DAG-induced activation of a PKC-dependent pathway.

Arachidonic acid metabolites induced β-adrenoceptor densitization in rat lung in vitro

1985 ◽  
Vol 30 (5) ◽  
pp. 799-809 ◽  
Author(s):  
Luisa Daffonchio ◽  
Maria Pia Abbracchio ◽  
Alicia Hernandez ◽  
Emanuela Giani ◽  
Flaminio Cattabeni ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Rat Lung ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites
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