Enhanced glomerular thromboxane A2 mediates some pathophysiologic effect of platelet-activating factor in rabbit nephrotoxic nephritis: Evidence from biochemical measurements and inhibitor trials

Daniela Macconi; Ariela Benigni; Marina Morigi; Angelo Ubiali; Silvia Orisio; Manuela Livio; Norberto Perico; Tullio Bertani; Giuseppe Remuzzi; Carlo Patrono

doi:10.5555/uri:pii:0022214389900243

Original article| Volume 113, ISSUE 5, P549-560, May 1989

Enhanced glomerular thromboxane A₂ mediates some pathophysiologic effect of platelet-activating factor in rabbit nephrotoxic nephritis: Evidence from biochemical measurements and inhibitor trials

Daniela Macconi
Daniela Macconi
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Ariela Benigni
Ariela Benigni
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Marina Morigi
Marina Morigi
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Angelo Ubiali
Angelo Ubiali
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Silvia Orisio
Silvia Orisio
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Manuela Livio
Manuela Livio
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Norberto Perico
Norberto Perico
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Tullio Bertani
Tullio Bertani
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Giuseppe Remuzzi
Giuseppe Remuzzi
Correspondence
Reprint requests: Giuseppe Remuzzi, MD, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24100 Bergamo, Italy.
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author
Carlo Patrono
Carlo Patrono
Affiliations
From the Mario Negri Institute for Pharmacological Research, Bergamo, Italy
From the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
From the National Research Council, Center of Cytopharmacology, University of Milan Milan, Italy
Search for articles by this author

DOI:https://doi.org/10.5555/uri:pii:0022214389900243

This paper is only available as a PDF. To read, Please Download here.

Abstract

Previous studies have shown that platelet-activating factor (PAF) receptor blocking has a protective effect on rabbit nephrotoxic nephritis (NTN). We examined whether arachidonic acid (AA) metabolism is altered in NTN and whether a PAF receptor antagonist has any influence on such changes. Rabbits injected with anti-glomerular basement membrane antiserum in the heterologous phase had a markedly increased glomerular thromboxane B₂ (TxB₂) production level, whereas no changes have been detected in glomerular 6-keto-prostaglandin F_1α (6-keto-PGF_1α) and prostaglandin E₂ (PGE₂). During the autologous phase of the disease, the glomerular TxB₂ level was even higher than in the heterologous phase. The level of 6-keto-PGF_1α was significantly lower than normal, and the level of PGE₂ was unchanged in respect to the basal values. The use of L-652,731 (a specific PAF receptor antagonist) reversed the abnormal generation of AA metabolites at glomerular level both in the heterologous and autologous phase of the disease. The effect of L-652,731 on AA metabolism is likely to be an indirect result of the PAF receptor blocking, because L-652,731 given to normal rabbits had no direct effect on glomerular AA metabolism. To assess whether the beneficial effect of L-652,731 in NTN is at least in part mediated by its capability of suppressing the excessive intrarenal synthesis of thromboxane A₂ (TxA₂), we compared the effect of L-652,731 with that of a selective TxA₂-synthase inhibitor (FCE-22178). FCE-22178 ameliorated the morphologic expression of rabbit NTN and reduced function deterioration. The protective effect of L-652,731 on proteinuria in the autologous phase and on glomerular filtration rate in both phases was superior to that of FCE-22178. We conclude that an excessive intraglomerular synthesis of TxA₂ occurs in rabbit NTN that can play a role in renal function deterioration. Both a specific PAF receptor antagonist and a TxA₂-synthase inhibitor reduced the exaggerated TxA₂ synthesis and favorably influenced the evolution of the disease.

Abbreviations:

AA (arachidonic acid), GBM (glomerular basement membrane), GFR (glomerular filtration rate), KRB (Krebs Ringer phosphate buffer), NTN (nephrotoxic nephritis), NTS (nephrotoxic serum), PAF (platelet-activating factor), PGE2 (prostaglandin E2), PGI2 (prostacyclin (prostaglandin I2)), PRP (platelet-rich plasma), TAC (threshold aggregating concentration), TxA2 (thromboxane A2), TxB2 (thromboxane B2)

To read this article in full you will need to make a payment

Purchase one-time access:

One-time access price info

For academic or personal research use, select 'Academic and Personal'
For corporate R&D use, select 'Corporate R&D Professionals'

Subscribe:

Already a print subscriber? Claim online access

Already an online subscriber? Sign in

Register: Create an account

Institutional Access: Sign in to ScienceDirect

References

- Pinckard RN
- McManus LM
- Hanahan DJ
Chemistry and biology of acetyl glyceryl ether phosphorylcholine (platelet-activating factor).
Adv Inflammation Res. 1982; 4: 147-169
- Google Scholar
- Camussi G
- Tetta C
- Coda R
- Segoloni GP
- Vercellone A
Platelet-activating factor-induced loss of glomerular anionic charges.
Kidney Int. 1984; 25: 73-81
- Google Scholar
- Pirotzky E
- Page C
- Morley J
- Bidault J
- Benveniste J
Vascular permeability induced by PAF-acether (platelet-activating factor) in the isolated perfused rat kidney.
Agents Actions. 1985; 16: 17-18
- Google Scholar
- Schiondorff D
- Goldwasser P
- Satriano JA
Synthesis of platelet-activating factor by isolated glomeruli and cultured mesangial cells of rat kidney [Abstract].
Clin Res. 1985; 33: 588A
- Google Scholar
- Schlondorff D
- Satriano JA
- Hagege J
- Perez J
- Baud L
Effect of platelet-activating factor and serum-treated zymosan on prostaglandin E2 synthesis, arachidonic acid release, and contraction of cultured rat mesangial cells.
J Clin Invest. 1984; 73: 1227-1231
- Google Scholar
- Ardaillou N
- Hagege J
- Nivez M-P
- Ardaillou R
- Schlondorff D
Vasoconstrictor-evoked prostaglandin synthesis in cultured human mesangial cells.
Am J Physiol. 1985; 248: F240-F246
- Google Scholar
- Ito S
- Camussi G
- Tetta C
- Milgrom F
- Andres G
Hyperacute renal allograft rejection in the rabbit. The role of platelet-activating factor and of cationic proteins derived from polymorphonuclear leukocytes and from platelets.
Lab Invest. 1984; 51: 148-161
- Google Scholar
- Camussi G
- Tetta C
- Deregibus MC
- Bussolino F
- Segoloni G
- Vercellone A
Platelet-activating factor (PAF) in experimentally-induced rabbit acute serum sickness: role of basophil-derived PAF in immune complex deposition.
J Immunol. 1982; 128: 86-94
- Google Scholar
- Hruby Z
- Lowry RP
- Blais D
Effect of platelet activating factor antagonist CV3988 in an autologous nephrotoxic nephritis model [Abstract].
Clin Res. 1986; 34: 602a
- Google Scholar
- Lianos EA
- Zanglis A
- Noble B
Renal immune injury: glomerular platelet activating factor (PAF) synthesis [Abstract].
Clin Res. 1987; 35: 551A
- Google Scholar
- Haliam TJ
- Sanchez A
- Rink TJ
Stimulus-response coupling in human platelets. Changes evoked by platelet-activating factor in cytoplasmic free calcium monitored with the fluorescent calcium indicator quin 2.
Biochem J. 1984; 218: 819-827
- Google Scholar
- Naccache PH
- Molski MM
- Volpi M
- Becker EL
- Sha'afi RI
Unique inhibitory profile of platelet activating factor induced calcium mobilization, polyphosphoinositide turnover and granule enzyme secretion in rabbit neutrophils towards pertussis toxin and phorbol ester.
Biochem Biophys Res Commun. 1985; 130: 677-684
- Google Scholar
- Bussolino F
- Aglietta M
- Sanavio F
- Stacchini A
- Lauri D
- Camussi G
Alkyl-ether phosphoglycerides influence calcium fluxes into human endothelial cells.
J Immunol. 1985; 135: 2748-2753
- Google Scholar
- Kester M
- Mené P
- Dubyak GR
- Dunn MJ
Elevation of cytosolic free calcium by platelet-activating factor in cultured rat mesangial cells.
FASEB J. 1987; 1: 215-219
- Google Scholar
- Weisman SM
- Felsen D
- Vaughan Jr, ED
Platelet-activating factor is a potent stimulus for renal prostaglandin synthesis: possible significance in unilateral ureteral obstruction.
J Pharmacol Exp Ther. 1985; 235: 10-15
- Google Scholar
- Bertani T
- Livio M
- Macconi D
- et al.
Platelet activating factor (PAF) as a mediator of injury in nephrotoxic nephritis.
Kidney Int. 1987; 31: 1248-1256
- Google Scholar
- Unanue ER
- Dixon FJ
Experimental glomerulonephritis: immunological events and pathogenetic mechanisms.
Adv Immunol. 1967; 6: 1-90
- Google Scholar
- Hwang S-B
- Lam M-H
- Biftu T
- Beattie TR
- Shen T-Y
Trans-2,5-Bis-(3,4,5-trimethoxyphenyl) tetrahydrofuran. An orally active specific and competitive receptor antagonist of platelet activating factor.
J Biol Chem. 1985; 260: 15639-15645
- Google Scholar
- Wu MS
- Biftu T
- Doebber TW
Inhibition of the platelet activating factor (PAF)-induced in vivo responses in rats by trans-2,5-(3,4,5- trimethoxyphenyl) tetrahydrofuran (L-652,731), a PAF receptor antagonist.
J Pharmacol Exp Ther. 1986; 239: 841-845
- Google Scholar
- Lowry OH
- Rosebrough NF
- Farr AG
- Randall RJ
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951; 193: 265-275
- Google Scholar
- Born GVR
- Cross MJ
The aggregation of blood platelets.
J Physiol. 1963; 168: 178-195
- Google Scholar
- Ciabattoni G
- Pugliese F
- Spaldi M
- Cinotti GA
- Patrono C
Radioimmunoassay measurement of prostaglandins E2 and F2 in human urine.
J Endocrinol Invest. 1979; 2: 173-182
- Google Scholar
- Read SM
- Northcote DH
Minimization of variation in the response to different proteins of the Coomassie blue G Dye-binding assay for protein.
Anal Biochem. 1981; 116: 53-64
- Google Scholar
- Bonsnes RW
- Taussky HH
The colorimetric determination of creatinine by the Jaffe reaction.
J Biol Chem. 1945; 158: 581-591
- Google Scholar
- Stork JE
- Dunn MJ
Hemodynamic roles of thromboxane A2 and prostaglandin E2 in glomerulonephritis.
J Pharmacol Exp Ther. 1985; 233: 672-678
- Google Scholar
- Schlondorff D
- Neuwirth R
Platelet-activating factor and the kidney.
Am J Physiol. 1986; 251: F1-F11
- Google Scholar
- Shaw JO
- Klusick SJ
- Hanahan DJ
Activation of rabbit platelet phospholipase and thromboxane synthesis by 1-0-hexadecyl-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor).
Biochim Biophys Acta. 1981; 663: 222-229
- Google Scholar
- Neuwirth R
- Singhal P
- Satriano JA
- Braquet P
- Shen TY
- Schlondorff D
Stimulation of PGE₂ synthesis by platelet-activating factor (PAF) in mesangial cells is inhibited by BN52021 and kadsurenone [Abstract].
in: Sixth International Conference on Prostaglandins and Related Compounds, Florence, Italy, 1986 Raven Press, New York1986: 320
- Google Scholar
- Stork JE
- Shen TY
- Dunn MJ
Stimulation of prostaglandin E2 and thromboxane B2 production in cultured rat mesangial cells by platelet activating factor: inhibition by a specific receptor antagonist [Abstract].
Kidney Int. 1985; 27: 267
- Google Scholar
- Scharschmidt LA
- Lianos E
- Dunn MJ
Arachidonate metabolites and the control of glomerular function.
in: 3rd ed. Fed Proc. 42. 1983: 3058-3063
- Google Scholar
- Jackson EK
- Heidemann HT
- Branch RA
- Gerkens JF
Low dose intrarenal infusions of PGE₂, PGI₂, and 6-keto-PGF_1α vasodilate the in vivo rat kidney.
Circ Res. 1982; 51: 67-72
- Google Scholar
- Schor N
- Ichikawa I
- Brenner BM
Mechanisms of action of various hormones and vasoactive substances on glomerular ultrafiltration in the rat.
Kidney Int. 1981; 20: 442-451
- Google Scholar
- Clive DM
- Stoff JS
Renal syndromes associated with nonsteroidal antiinflammatory drugs.
N Engl J Med. 1984; 310: 563-572
- Google Scholar
- Lianos EA
- Noble B
Glomerular arachidonate-5 lipoxygenation in active (A) and Passive (P) Heymann nephritis [Abstract].
Kidney Int. 1986; 31: 277
- Google Scholar
- Sraer J
- Rigaud M
- Bens M
- Rabinovitch H
- Ardaillou R
Metabolism of arachidonic acid via the lipoxygenase pathway in human and murine glomeruli.
J Biol Chem. 1983; 258: 4325-4330
- Google Scholar
- Jim K
- Hassid A
- Sun F
- Dunn MJ
Lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells and cortical tubules.
J Biol Chem. 1982; 257: 10294-10299
- Google Scholar
- Badr KF
- Baylis C
- Pfeffer JM
- et al.
Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C₄ in the rat.
Circ Res. 1984; 54: 492-499
- Google Scholar
- Filep J
- Rigter B
- Frolich JC
Vascular and renal effects of leukotriene C4 in conscious rats.
Am J Physiol. 1985; 249: F739-F744
- Google Scholar
- Badr KF
- Brenner BM
- Wasserman M
- Ichikawa I
Evidence for local glomerular actions of leukotriene D4 (LTD4) [Abstract].
Kidney Int. 1986; 29: 328
- Google Scholar
- Lianos EA
- Andres GA
- Dunn MJ
Glomerular prostaglandin ad thromboxane synthesis in rat nephrotoxic serum nephritis. Effects on renal hemodynamics.
J Clin Invest. 1983; 72: 1439-1448
- Google Scholar
- Thomson NM
- Holdsworth SR
- Glasgow EF
- Atkins RC
The macrophage in the development of experimental crescentic glomerulonephritis. Studies using tissue culture and electron microscopy.
Am J Pathol. 1979; 94: 223-240
- Google Scholar
- Delaini F
- Tagliaferri M
- Macconi D
- Lupini C
- Perico N
- Remuzzi G
Platelet activating factor (PAF) as a mediator of proteinuria in isolated perfused kidney (IPK) [Abstract].
in: Tenth International Congress of Nephrology, London, 1987 The Alden Press, Oxford1987: 263
- Google Scholar
- Perico N
- Delaini F
- Tagliaferri M
- et al.
The effect of platelet-activating factor and its specific receptor antagonist on glomerular permeability to proteins in isolated perfused rat kidney.
Lab Invest. 1988; 58: 163-171
- Google Scholar
- Hébert RL
- Sirois P
- Braquet P
- Plante GE
Hemodynamic effects of PAF-acether on the dog kidney.
Prostaglandins Leukotrienes Med. 1987; 26: 189-202
- Google Scholar
- Scherf H
- Nies AS
- Schwertschlag U
- Hughes M
- Gerber JG
Hemodynamic effects of platelet activating factor in the dog kidney in vivo.
Hypertension. 1986; 8: 737-742
- Google Scholar
- Sraer J
- Foidart J
- Chansel D
- Mahieu P
- Kouznetsov B
- Ardaillou R
Prostaglandin synthesis by mesangial and epithelial glomerular cultured cells.
FEBS Lett. 1979; 104: 420-424
- Google Scholar

Article info

Publication history

Accepted: January 12, 1989

Received in revised form: December 2, 1988

Received: June 2, 1988

Identification

DOI: https://doi.org/10.5555/uri:pii:0022214389900243

Copyright

ScienceDirect

Access this article on ScienceDirect

Property	Value
Status
Version
Ad File
Disable Ads Flag
Environment
Moat Init
Moat Ready
Contextual Ready
Contextual URL
Contextual Initial Segments
Contextual Used Segments
AdUnit
SubAdUnit
Custom Targeting
Ad Events
Invalid Ad Sizes