Comparative effects of platelet activating factor, leukotriene D4 and histamine on guinea pig trachea, bronchus and lung parenchyma

1987 ◽  
Vol 33 (2) ◽  
pp. 199-208 ◽  
Author(s):  
S. Jancar ◽  
P. Thériault ◽  
P. Braquet ◽  
P. Sirois
Keyword(s):  
Guinea Pig ◽  
Platelet Activating Factor ◽  
Lung Parenchyma ◽  
Leukotriene D4

Histamine, leukotriene D4 and platelet-activating factor in guinea pig passive cutaneous anaphylaxis

1991 ◽  
Vol 204 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Vivian B. Weg ◽  
Malcolm L. Watson ◽  
Renato S.B. Cordeiro ◽  
Timothy J. Williams
Keyword(s):  
Guinea Pig ◽  
Platelet Activating Factor ◽  
Passive Cutaneous Anaphylaxis ◽  
Leukotriene D4

Anatomic basis for species differences in peripheral lung strip contraction to PAF

1990 ◽  
Vol 259 (2) ◽  
pp. L81-L86 ◽  
Author(s):  
M. Halonen ◽  
A. M. Dunn ◽  
J. D. Palmer ◽  
L. M. McManus
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Platelet Activating Factor ◽  
Contractile Element ◽  
Leukotriene D4 ◽  
Pleural Surface ◽  
Peripheral Lung ◽  
Lower Lung ◽  
Anatomic Basis ◽  
Lung Lobes

Platelet-activating factor (PAF) is a very potent contractile agonist in guinea pig peripheral lung strips but is without effect on rabbit peripheral lung strips. Histological examination of guinea pig peripheral lung strips revealed a layer of smooth muscle cells in the visceral pleura that is not present in rabbit peripheral lung strips. Removal of the pleural surface of the guinea pig peripheral lung strips eliminated the ability of these tissues to contract to PAF, and the (removed) thin pleural strip contracted to PAF in a manner similar to that of intact strips. Removal of the pleural surface did not prevent these tissues from contracting to histamine or leukotriene D4 (LTD4), although potency of these agonists was somewhat reduced. The pleural smooth muscle cell layer is present throughout the pleural lining of the guinea pig lung but is thicker in lower than in upper lobes. PAF contractility is also reduced in upper compared with lower lung lobes. Thus we suggest that the pleural smooth muscle is the critical contractile element for PAF contraction of guinea pig peripheral lung strips, whereas other agonists such as histamine and LTD4 contract additional elements in these tissues.

Influence of platelet-activating factor on leukotriene D4-induced contractions of the guinea pig parenchymal strip

1989 ◽  
Vol 67 (4) ◽  
pp. 315-321 ◽  
Author(s):  
A. Yaghi ◽  
J. T. Hamilton ◽  
N. A. M. Paterson
Keyword(s):  
Guinea Pig ◽  
Potassium Chloride ◽  
Platelet Activating Factor ◽  
Nordihydroguaiaretic Acid ◽  
Leukotriene D4 ◽  
Lipoxygenase Inhibitors ◽  
Thromboxane Synthase Inhibitor ◽  
Respiratory Events ◽  
Paf Receptor ◽  
Synthase Inhibitor

Platelet-activating factor (PAF) and sulphidopeptide leukotrienes, such as leukotriene D4 (LTD4), are potent constrictors that are probably released simultaneously in a variety of inflammatory respiratory events. The purpose of the present study was to determine whether LTD4-induced contractions of guinea pig parenchymal lung strips (GPPS) are modified in the presence of PAF. The contractile responses of isolated GPPS to cumulative doses of LTD4, acetylcholine, histamine, and potassium chloride in the presence of PAF (0.1 nM, 0.1 μM) were compared with parallel controls. There was no significant alteration of the response to acetylcholine and potassium chloride and the PAF-induced inhibition of the response to histamine, although significant, was not concentration dependent. In contrast, PAF in a concentration range from 0.1 nM to 1.0 μM caused a marked, concentration-dependent reduction of LTD4-induced contractions. Pretreatment with the PAF receptor antagonist, BN52021, prevented the attenuation of LTD4-induced contraction by PAF. The attenuation of LTD4-induced contraction by PAF was also prevented by pretreatment with indomethacin or with the thromboxane synthase inhibitor U63,557A, but not by pretreatment with the lipoxygenase inhibitors BW755c or nordihydroguaiaretic acid. Thus inhibition of LTD4-induced GPPS contraction by PAF is receptor dependent and probably secondary to thromboxane generation. The respiratory smooth muscle response to leukotrienes may be modified significantly by concomitant PAF release.Key words: platelet-activating factor, leukotriene D4, lung, parenchymal strip, guinea pig.

Leukotriene D4 and platelet-activating factor – acether antagonists on allergic and arachidonic acid-induced reactions in guinea pig airways

1989 ◽  
Vol 67 (5) ◽  
pp. 483-490 ◽  
Author(s):  
John F. Burka ◽  
Heather Briand ◽  
Peter Scott-Savage ◽  
Franco M. Pasutto
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Guinea Pig ◽  
Receptor Antagonist ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
Leukotriene D4 ◽  
Total Inhibition ◽  
Low Concentrations ◽  
Lung Parenchymal Strip

Arachidonic acid (AA) and ovalbumin (OA) were used to induce contractions of sensitized guinea pig tracheal spiral (indomethacin-pretreated) and lung parenchymal strip preparations. This model was used to examine the properties of three leukotriene (LT) D4 antagonists and a platelet-activating factor (PAF)–acether receptor antagonist. The three LTD4 antagonists, L-649,923, FPL 57231, and LY163443, inhibited AA-induced contractions of indomethacin-pretreated tracheal spirals selectively. The PAF–acether antagonist, L-652,731, did not inhibit AA-induced contractions of either trachea or parenchyma. This confirmed that AA-induced contractions of trachea involved release and activity of LTD4. The LTD4 antagonists and L-652,731 partially inhibited OA-induced contractions of both trachea and parenchyma. When L-649,923 and L-652,731 or FPL 57231 and L-652,731 were combined, an additive inhibitory effect on OA-induced contractions was observed. When LY163443 and L-652,731 were combined, the inhibitory effect was synergistic. This may be due to the additional effect of LY163443 to inhibit phosphodiesterase. Total inhibition of OA-induced contractions was obtainable with relatively low concentrations when a LTD4 and PAF–acether antagonist were combined. These results suggested that LTD4 and PAF–acether may be the two major mediators in our model of allergic bronchospasm. The LTD4 and PAF–acether antagonists had the capacity to decrease baseline tone, even on tissues that were already relaxed with indomethacin, suggesting that LTD4 and PAF–acether may contribute to intrinsic tone in airway smooth muscle.Key words: leukotriene D4, platelet-activating factor, airway smooth muscle, antagonists, allergic bronchospasm.

Release of tachykinins by histamine, methacholine, PAF, LTD4, and substance P from guinea pig lungs

1991 ◽  
Vol 261 (6) ◽  
pp. L449-L455 ◽  
Author(s):  
M. A. Martins ◽  
S. A. Shore ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Platelet Activating Factor ◽  
Neutral Endopeptidase ◽  
Neurokinin A ◽  
Opening Pressure ◽  
Leukotriene D4 ◽  
Airway Opening

The release of substance P- and neurokinin A-like immunoreactivities (SP-LI and NKA-LI) after tracheal infusion of histamine, methacholine, leukotriene D4, and platelet-activating factor was measured in isolated guinea pig lungs superfused through the trachea. Infusion of each of these agonists was associated with a significant (P less than 0.05) increase in the recovery of both SP-LI and NKA-LI from lung perfusates compared with preinfusion baseline recoveries of these peptides. After infusion of bronchoactive mediators, approximately 4-15 times more NKA-LI than SP-LI was recovered from the lung superfusate. Coincident with the release of neuropeptides, mediator infusion was accompanied by an increase in airway opening pressure (Pao). Addition to the perfusate of the neutral endopeptidase inhibitor thiorphan, 1 microM increased the change in Pao induced by histamine (10(-8) mol, P less than 0.005) and methacholine (10(-8) mol, P less than 0.02) and increased the recovery of NKA-LI (P less than 0.05 for histamine and methacholine). Addition of isoproterenol to the perfusion buffer reduced, but did not abolish, either the Pao response or the increased recovery of NKA-LI (P less than 0.05) observed after histamine infusion. We conclude that bronchoactive agonists have the capacity to release both SP-LI and NKA-LI, and we speculate that NKA contributes to the bronchomotor response observed in response to histamine or methacholine.

Mechanism of action of platelet-activating factor on guinea-pig lung parenchyma strips

1988 ◽  
Vol 66 (9) ◽  
pp. 1187-1191 ◽  
Author(s):  
Sonia Jancar ◽  
Patrick Thériault ◽  
Brigitte Provençal ◽  
Solange Cloutier ◽  
Pierre Sirois
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Acid Metabolism ◽  
Contractile Response ◽  
Platelet Activating Factor ◽  
Lung Parenchyma ◽  
Arachidonic Acid Metabolism ◽  
Lipoxygenase Inhibitor ◽  
Lipoxygenase Pathway ◽  
Thromboxane Synthetase

The contribution of thromboxane A2 to platelet-activating factor (PAF)induced contraction of guinea-pig lung parenchyma strips (GPLPS) was investigated using an experimental design that allowed us to record the contractions of the tissues in parallel with the determination of thromboxane B2 (TXB2) levels in the organ baths by enzyme immunoassay. It was found that the first injection of PAF induced the contraction of GPLPS and the release of TXB2. Following subsequent additions of PAF to the same tissue, the contractile response was abolished but TXB2 levels were not significantly reduced. Pretreatment of the tissue with the thromboxane synthetase inhibitor OKY-046 (3.5, 170, and 350 μM) strongly inhibited the release of TXB2 but had no effect on the contraction of the tissues induced by PAF. The mechanism of PAF-induced contraction of GPLPS was further investigated using several drugs that interfere with arachidonic acid metabolism. It was found that pretreatment of the tissues with the cyclooxygenase and thromboxane synthetase inhibitors indomethacin (2.8, 28, and 56 μM) and OKY-046 (170 μM) or with the thromboxane antagonist SKF-88046 (1.25 and 12.5 μM) had no significant effect on the contractile response to PAF. The compound L-655,240 (2.5, 25, and 50 μM), which acts simultaneously as an antagonist of thromboxane and inhibitor of lipoxygenase, significantly reduced GPLPS contractions induced by PAF. Another lipoxygenase inhibitor, nordihydroguaiaretic acid (33 μM), and the inhibitor of both pathways of arachidonic acid metabolism, BW775c (110 μM), both reduced PAF-induced contractions of GPLPS. We conclude that although PAF induces release of thromboxane from GPLPS, this mediator does not contribute significantly to the myotropic activity of PAF, which seems to be mediated by products of the lipoxygenase pathway.

Does thromboxane mediate the indirect contractile action of leukotriene D4 in guinea-pig isolated lung parenchyma under equilibrium conditions?

1987 ◽  
Vol 65 (7) ◽  
pp. 1467-1477 ◽  
Author(s):  
Mark A. Giembycz ◽  
Ian W. Rodger
Keyword(s):  
Guinea Pig ◽  
Direct Action ◽  
Maximum Amplitude ◽  
Lung Parenchyma ◽  
Isometric Tension ◽  
High Concentration ◽  
Equilibrium Conditions ◽  
Leukotriene D4 ◽  
Tension Development ◽  
Isolated Lung

The role that thromboxane A2 plays in contractions induced by leukotriene D4 in guinea-pig isolated lung parenchyma was investigated under equilibrium conditions. Lung tissue generated thromboxane A2 and prostacyclin spontaneously as evidenced by the slow accumulation of their biologically inactive metabolites, thromboxane B2 and 6-keto-prostaglandin F1α, in the bathing buffer. Challenge of guinea-pig lung parenchyma with a high concentration (EC90 for tension generation) of leukotriene D4 (200 nM) produced a biphasic contraction of the tissue that consisted of an initial rapid increase in isometric tension followed by a slowly developing, well-sustained contracture. In addition, leukotriene D4 (200 nM) effected a transient increase (over basal) in the generation of thromboxane A2 and prostacyclin that lagged significantly behind the tension response. Kinetic analysis of the mechanical and eicosanoid-generating effect of leukotriene D4 revealed that tension development could be suitably fitted to a biexponential function, whilst the release of both eicosanoids from the lung occurred monoexponentially. Pretreatment of the lung with the cyclooxygenase inhibitor, flurbiprofen, which effectively abolished both the spontaneous and the leukotriene D4-stimulated eicosanoid biosynthesis, significantly reduced both the first order rate coefficient of the first exponent and the maximum amplitude of this function with respect to control. This change in the kinetics describing leukotriene D4-induced contractions was explained by the fact that the initial rate of tension development was markedly reduced following pretreatment of the lung with flurbiprofen. Neither the inhibitor of thromboxane synthetase, dazmegrel, which selectively inhibited (by 95%) leukotriene D4-stimulated thromboxane A2 formation, nor blockade of 11α,9α-epoxymethano-prostaglandin H2 (U-46619)-sensitive (thromboxane A2) receptors with either AH 23848 or EP 092 affected the profile of leukotriene D4-induced tension development in guinea-pig lung. It is concluded that a high concentration of leukotriene D4 (200 nM) contracts guinea-pig lung by both a direct and indirect mechanism. Initially, a rapid short-lived contraction of the lung is manifest which is dependent, in part, upon the synthesis and release of cyclooxygenase product(s) other than thromboxane A2. This initial response occurs coincidently with, and is subsequently followed by, the development of a tonic well-sustained contracture that is the result of a direct action of leukotriene D4 on the contractile cells that comprise the lung.

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