Group I secreted PLA2 and arachidonic acid metabolites in the maintenance of cat LES tone.

Spontaneous tone of in vitro lower esophageal sphincter (LES) circular muscle is associated with elevated levels of arachidonic acid (AA), PGF(2alpha), and increased [35S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding to Gq-, Gi3-, and G(i1/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 A2 antagonist SQ-29548. In addition, pertussis toxin (PTX) reduced LES tone, confirming a role of PTX-sensitive G proteins in maintenance of LES tone. PGF(2alpha) contracted LES smooth muscle (strips and cells) and increased [35S]GTPgammaS binding to Gq and Gi3 in solubilized LES circular muscle membranes. PGF(2alpha)-induced contraction of LES permeable muscle cells was inhibited by Gq and Gi3 but not by G(i1/i2) and Go antibodies. The thromboxane A2 analog U-46619 contracted LES smooth muscle and increased Gq binding. U-46619-induced contraction was inhibited by Gq but not by Gi3, G(i1/i2), and Go antibodies. LES tone and [(35)S]GTPgammaS binding were significantly reduced by indomethacin. We conclude that group I sPLA2 may mediate "spontaneous" LES tone by producing AA, which is metabolized to PGF(2alpha) and thromboxane A2. These AA metabolites activate receptors linked to Gi3 and Gq to maintain LES contraction.

[1]  S. Katsumura,et al.  pH dependence of the reaction rate of p-bromophenacyl bromide and of the binding constants of Ca2+ and an amide-type substrate analog to bovine pancreatic phospholipase A2. , 1998, Archives of biochemistry and biophysics.

[2]  J. Regan,et al.  Prostanoid receptor heterogeneity through alternative mRNA splicing. , 1998, Life sciences.

[3]  U. Sohn,et al.  Acute experimental esophagitis activates a second signal transduction pathway in cat smooth muscle from the lower esophageal sphincter. , 1997, The Journal of pharmacology and experimental therapeutics.

[4]  J. Tischfield.  A Reassessment of the Low Molecular Weight Phospholipase A2 Gene Family in Mammals* , 1997, The Journal of Biological Chemistry.

[5]  U. Sohn,et al.  Experimental esophagitis affects intracellular calcium stores in the cat lower esophageal sphincter. , 1997, The American journal of physiology.

[6]  R. Levy,et al.  Phospholipase A2 has a role in proliferation but not in differentiation of HL-60 cells. , 1997, Biochimica et biophysica acta.

[7]  E. Dennis,et al.  The growing phospholipase A2 superfamily of signal transduction enzymes. , 1997, Trends in biochemical sciences.

[8]  Y. Matsuzawa,et al.  Phospholipase A2 stimulation of rat intestinal epithelial cell (IEC-6) migration. , 1996, The American journal of physiology.

[9]  U. Sohn,et al.  Protein kinase C mediates spontaneous tone in the cat lower esophageal sphincter. , 1996, The Journal of pharmacology and experimental therapeutics.

[10]  G. Makhlouf,et al.  Somatostatin Receptor-mediated Signaling in Smooth Muscle ACTIVATION OF PHOSPHOLIPASE C- 3 BY G AND INHIBITION OF ADENYLYL CYCLASE BY G AND G o , 1996 .

[11]  M. Lazdunski,et al.  Identification of the Binding Domain for Secretory Phospholipases A2 on Their M-type 180-kDa Membrane Receptor * , 1995, The Journal of Biological Chemistry.

[12]  R. Varhol,et al.  Kinetics of Thapsigargin- Ca-ATPase (Sarcoplasmic Reticulum) Interaction Reveals a Two-step Binding Mechanism and Picomolar Inhibition (*) , 1995, The Journal of Biological Chemistry.

[13]  R. Armstrong,et al.  Aspects of the thromboxane receptor system. , 1995, General pharmacology.

[14]  M. Lazdunski,et al.  The Human 180-kDa Receptor for Secretory Phospholipases A2 , 1995, The Journal of Biological Chemistry.

[15]  U. Sohn,et al.  Agonist-independent, muscle-type-specific signal transduction pathways in cat esophageal and lower esophageal sphincter circular smooth muscle. , 1995, The Journal of pharmacology and experimental therapeutics.

[16]  H. Toh,et al.  Molecular evolution of receptors for eicosanoids , 1995, FEBS letters.

[17]  M. Lazdunski,et al.  Structural Elements of Secretory Phospholipases A2 Involved in the Binding to M-type Receptors (*) , 1995, The Journal of Biological Chemistry.

[18]  S. Narumiya,et al.  Functional reconstitution of platelet thromboxane A2 receptors with Gq and Gi2 in phospholipid vesicles. , 1994, Molecular pharmacology.

[19]  U. Sohn,et al.  Role of 100-kDa cytosolic PLA2 in ACh-induced contraction of cat esophageal circular muscle. , 1994, The American journal of physiology.

[20]  O. Berg,et al.  Inhibition of phospholipase A2 , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[21]  M. Gelb,et al.  Tight binding inhibitors of 85-kDa phospholipase A2 but not 14-kDa phospholipase A2 inhibit release of free arachidonate in thrombin-stimulated human platelets. , 1994, The Journal of biological chemistry.

[22]  E. Dennis.  Diversity of group types, regulation, and function of phospholipase A2. , 1994, The Journal of biological chemistry.

[23]  R. A. Coleman,et al.  A novel inhibitory prostanoid receptor in piglet saphenous vein. , 1994, Prostaglandins.

[24]  G. Schultz,et al.  G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  U. Sohn,et al.  Distinct muscarinic receptors, G proteins and phospholipases in esophageal and lower esophageal sphincter circular muscle. , 1993, The Journal of pharmacology and experimental therapeutics.

[26]  B. Wolf,et al.  Transient activation of calcium-dependent phospholipase A2 by insulin secretagogues in isolated pancreatic islets. , 1993, Biochemistry.

[27]  C. Leslie,et al.  Regulation of phospholipase A2 activation by phosphorylation in mouse peritoneal macrophages. , 1993, The Journal of biological chemistry.

[28]  J. Nishihira,et al.  Effect of vitamin E on arachidonic acid-release in rat peritoneal macrophages. , 1993, Biochimica et biophysica acta.

[29]  M. Murakami,et al.  Mammalian non-pancreatic phospholipases A2. , 1993, Biochimica et biophysica acta.

[30]  R. Gross,et al.  Arachidonic acid release from aortic smooth muscle cells induced by [Arg8]vasopressin is largely mediated by calcium-independent phospholipase A2. , 1993, The Journal of biological chemistry.

[31]  R. Graham,et al.  Coupling of expressed alpha 1B- and alpha 1D-adrenergic receptor to multiple signaling pathways is both G protein and cell type specific. , 1993, Molecular pharmacology.

[32]  Y. Sugimoto,et al.  Prostanoid receptors and their biological actions. , 1993, Progress in lipid research.

[33]  H. Arita,et al.  Effect of pancreatic type phospholipase A2 on isolated porcine cerebral arteries via its specific binding sites , 1992, FEBS letters.

[34]  I. Nishimoto,et al.  Measurement of GTPγS binding to specific G proteins in membranes using G‐protein antibodies , 1992 .

[35]  J. L. Bobbitt,et al.  Porcine pancreatic phospholipase A2-induced contractions of guinea pig lung pleural strips. , 1992, European journal of pharmacology.

[36]  M. Kaminski,et al.  Hsp27 is a mediator of sustained smooth muscle contraction in response to bombesin. , 1991, Biochemical and biophysical research communications.

[37]  M. Lazdunski,et al.  Identification of different receptor types for toxic phospholipases A2 in rabbit skeletal muscle , 1991, FEBS letters.

[38]  K. Matsumoto,et al.  Novel proliferative effect of phospholipase A2 in Swiss 3T3 cells via specific binding site. , 1991, The Journal of biological chemistry.

[39]  S. Hall.  Thromboxane A2 receptor antagonists , 1991, Medicinal research reviews.

[40]  A. Shenker,et al.  The G protein coupled to the thromboxane A2 receptor in human platelets is a member of the novel Gq family. , 1991, Transactions of the Association of American Physicians.

[41]  Y. Hannun,et al.  Role of phospholipases in generating lipid second messengers in signal transduction 1 , 1991, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  M. Lazdunski,et al.  Identification and purification of a very high affinity binding protein for toxic phospholipases A2 in skeletal muscle. , 1990, The Journal of biological chemistry.

[43]  G. FitzGerald,et al.  The response to thromboxane A2 analogues in human platelets. Discrimination of two binding sites linked to distinct effector systems. , 1990, The Journal of biological chemistry.

[44]  M. Lazdunski,et al.  Identification and properties of very high affinity brain membrane-binding sites for a neurotoxic phospholipase from the taipan venom. , 1989, The Journal of biological chemistry.

[45]  J. D. de Jong,et al.  Immunoaffinity purification, partial sequence, and subcellular localization of rat liver phospholipase A2. , 1989, The Journal of biological chemistry.

[46]  P. Halushka,et al.  Thromboxane, prostaglandin and leukotriene receptors. , 1989, Annual review of pharmacology and toxicology.

[47]  H. Tojo,et al.  A phospholipase A2 in the supernatant fraction of rat spleen. Its similarity to rat pancreatic phospholipase A2. , 1988, The Journal of biological chemistry.

[48]  M. Ogawa,et al.  Distribution of immunoreactive pancreatic phospholipase A2 (IPPL-2) in various human tissues. , 1987, Research communications in chemical pathology and pharmacology.

[49]  Y. Urade,et al.  Content and formation of prostaglandins and distribution of prostaglandin-related enzyme activities in the rat ocular system. , 1987, Biochimica et biophysica acta.

[50]  G. Dorn,et al.  Cultured human vascular smooth muscle cells with functional thromboxane A2 receptors: measurement of U46619-induced 45calcium efflux. , 1987, Circulation research.

[51]  P. Bradford,et al.  Stoichiometry of contraction and Ca2+ mobilization by inositol 1,4,5-trisphosphate in isolated gastric smooth muscle cells. , 1986, The Journal of biological chemistry.

[52]  J. Seilhamer,et al.  Pancreatic phospholipase A2: isolation of the human gene and cDNAs from porcine pancreas and human lung. , 1986, DNA.

[53]  M. Mitchell,et al.  Prostaglandin E2 9-ketoreductase activity in human decidua vera tissue. , 1986, American journal of obstetrics and gynecology.

[54]  K. Fukuo,et al.  Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells. , 1986, Biochemical and biophysical research communications.

[55]  P. Weber,et al.  Prostaglandin endoperoxide analogues stimulate phospholipase C and protein phosphorylation during platelet shape change. , 1985, Blood.

[56]  T. Rink,et al.  What turns platelets on , 1984 .

[57]  D. Macintyre,et al.  Thromboxane-induced phosphatidate formation in human platelets. Relationship to receptor occupancy and to changes in cytosolic free calcium. , 1984, The Biochemical journal.

[58]  J. Behar,et al.  Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation. , 1984, The Journal of clinical investigation.

[59]  J. Behar,et al.  Neural control of the lower esophageal sphincter in the cat: studies on the excitatory pathways to the lower esophageal sphincter. , 1982, Gastroenterology.

[60]  J. Behar,et al.  Lower esophageal sphincter mechanics: anatomic and physiologic relationships of the esophagogastric junction of cat. , 1982, Gastroenterology.

[61]  S. Greenberg.  Effect of prostacyclin and 9a, 11a-epoxymethanoprostaglandin H2 on calcium and magnesium fluxes and tension development in canine intralobar pulmonary arteries and veins. , 1981, The Journal of pharmacology and experimental therapeutics.

[62]  K. H. Kalk,et al.  Active site and catalytic mechanism of phospholipase A2 , 1981, Nature.

[63]  E. Anggard,et al.  Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals. , 1980, Prostaglandins.

[64]  S. Sarna,et al.  Prostaglandins and myogenic control of tension in lower esophageal sphincter in vitro. , 1979, Prostaglandins.

[65]  S. Sarna,et al.  Role of endogenous prostaglandins in regulating the tone of opossum lower esophageal sphincter in vivo. , 1979, Prostaglandins.

[66]  S. Sarna,et al.  Prostaglandins and tetrodotoxin-insensitive relaxation of opossum lower esophageal sphincter. , 1979, The American journal of physiology.

[67]  G. Rangaraj,et al.  Distribution of prostaglandin biosynthetic pathways in organs and tissues of the fetal lamb. , 1978, Biochimica et biophysica acta.

[68]  S. Rattan,et al.  Genesis of basal sphincter pressure: effect of tetrodotoxin on lower esophageal sphincter pressure in opossum in vivo. , 1976, Gastroenterology.

[69]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[70]  J. Harper,et al.  Relationship between concentration of prostaglandin F (PGF) in the oviduct and egg transport in rabbits. , 1975, Biology of reproduction.

[71]  J. Conklin,et al.  Physiologic specialization at esophagogastric junction in three species. , 1973, The American journal of physiology.

[72]  S. Rattan,et al.  Comparison of the effects of prostaglandins E1, E2, and A2, and of hypovolumic hypotension on the lower esophageal sphincter. , 1973, Gastroenterology.

[73]  J. Christensen,et al.  Some physiological characteristics of the esophagogastric junction in the opossum. , 1973, Gastroenterology.

[74]  S. Rattan,et al.  Mechanism of the lower esophageal sphincter relaxation. Action of prostaglandin E 1 and theophylline. , 1973, The Journal of clinical investigation.