Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P25105 (PAF receptor)
 1,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The action of platelet activating factor in the rat brain was detected by Evans blue staining after injection of PAF into the rat brain. The results show that PAF increased the Evans blue staining of the brain, but no staining was observed without prior injection of PAF. Meanwhile, PAF was shown to stimulate the release of 14C-arachidonic acid (14C-AA) in the cerebral microvascular smooth muscle cells (CMSMC). SZ-1, a new synthetic drug, dose-dependently inhibited the Evans blue staining of the rat brain and the PAF induced 14C-AA release in CMSMC. These results indicate that the action of PAF in the rat brain might be related to the stimulation of AA release. SZ-1 may antagonize the PAF receptor and protect the brain from PAF induced damage.
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PMID:[Effects of platelet activating factor on the cerebrovascular permeability in rats and the protection by drug]. 129 34

Platelet activating factor (PAF) is a phospholipid mediator of inflammation and vascular leakage that may be important in the etiology of asthma. We and others have demonstrated that PAF causes vascular leakage in the rat trachea. In the present study, we attempted to determine how PAF mediates this effect. Vascular leakage was quantitated by measuring the amount of intravascular Evans blue dye extravasated into tracheal tissue. Intravenously administered PAF increased vascular leakage, although Lyso-PAF and Enantio-PAF had no effect. PAF-induced vascular leakage was inhibited in a dose-dependent fashion by the PAF receptor blocker WEB 2086. However, PAF-induced vascular leakage was not inhibited by blockade of cyclooxygenase/lipoxygenase, calmodulin, calcium channels, protein kinase C, histamine receptors, or by destruction of peptidergic sensory nerves. We conclude that PAF causes vascular leakage in the rat trachea by a stereospecific receptor-mediated mechanism that does not depend on arachidonic acid metabolites, calcium, protein kinase C, histamine, or peptidergic sensory nerves.
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PMID:Mechanism of platelet activating factor-induced vascular leakage in the rat trachea. 135 25

1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.5. When low doses of endothelin-1 (0.1 nmolkg-')and PAF (0.19nmolkg-')were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin-1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.6. Combined administration of higher doses of endothelin-1 (1nmolkg-') and PAF (1.9nmolkg-') resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin-1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin-1 and PAF resulted in a slight, but significant increase in MABP.7. The present findings show that endothelin-1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin-1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.
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PMID:Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor. 166 86

Platelet activating factor (PAF) released by many cell types is involved in several steps of inflammatory reactions in various organs including the eye. It has been reported that some effects of PAF could be mediated by arachidonic acid metabolites generated after PAF-receptor interaction. In the study we investigated the protective effect of CBS-113A, a dual inhibitor of 5-lipoxygenase/cyclooxygenase in PAF-induced conjunctivitis in the rabbit. Moreover, the characterization of the icosanoid potentially mediating the PAF activity has been performed by using specific pharmacological agents. Subconjunctival injection of PAF (10-1000 ng) provoked Evans' blue extravasation measured in tissues within 30 min. Simultaneous injection of a PAF antagonist (BN 50730) inhibited the dye leakage, showing specific PAF receptor-mediated vascular reaction. CBS-113A applied in eye drops also inhibited Evans' blue extravasation. By contrast, indometacin administered either topically or by subconjunctival injection was not effective in reducing the effect of PAF. These results suggesting the involvement of a 5-lipoxygenase metabolite were confirmed by the effectiveness of local injection of SKF 104353, a specific leukotriene D4 antagonist. The present study shows that PAF-induced plasma leakage in conjunctivitis is mediated by peptido-leukotrienes.
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PMID:PAF-induced conjunctivitis in the rabbit is mediated by peptido-leukotrienes. 196 92

A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 microgram, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0.1 microgram of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0.1 microgram of PAF. In contrast, the PAF-induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L-652,731, a dose as low as 5 mg kg-1 eliciting a significant inhibition. The topical administration of L-652,731, (two doses of 100 micrograms as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co-injected subconjunctivally with 0.1 microgram of PAF, a dose as low as 3 micrograms evoking a significant blockade. The topical administration of 0.1 microgram of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.
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PMID:A study of PAF-induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L-652,731. 289 30

Platelet-activating factor (PAF) is a proinflammatory mediator known to elicit changes in airway reactivity and vascular permeability, and it may also have a role in the development and progression of acute respiratory distress syndrome and asthma. We have developed a mouse model to test the hypothesis that these traits were controlled by a single gene and were mechanistically related. We further hypothesized that there was a relationship between PAF-induced hyperreactivity and baseline reactivity to acetylcholine (ACh). Among eight inbred strains of mice that exhibited significant interstrain variation in ACh reactivity, intravenous PAF induced 16 to 278% increases in reactivity to ACh (25 micrograms/kg). PAF also elicited 95 to 307% increases in lung permeability as measured by Evans blue extravasation. Both reactivity and permeability changes induced by PAF were blocked by a PAF receptor antagonist (L-659,989). Strain distribution patterns for baseline reactivity to ACh and PAF-induced hyperreactivity and lung permeability were not significantly concordant, and suggest that the variables were not interdependent. Progeny derived from AKR/J (PAF hyperresponsive) and C3H/HeJ (PAF hyporesponsive) mice were characterized for their PAF responsiveness as determined by PAF-induced hyperreactivity and hyperpermeability. The ratios of hyperresponsive and hyporesponsive phenotypes in outcross progeny were compared to those predicted for Mendelian inheritance and assessed for relatedness by chi 2 and cosegregation analyses. Results suggested that PAF-induced hyperreactivity was controlled by a single gene, but PAF-induced hyperpermeability was controlled by a more complicated interaction of factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Susceptibility to platelet-activating factor-induced airway hyperreactivity and hyperpermeability: interstrain variation and genetic control. 757 95

In the present study, we asked whether platelet-activating factor (PAF) mediates the ozone-induced increase in airway microvascular leakage. To answer this question, we examined the effect of a PAF receptor antagonist on the ozone-induced increase in airway microvascular leakage quantified by the extravasation of Evans blue dye in the guinea pig trachea and main bronchi. Guinea pigs were pretreated with the PAF receptor antagonist, E6123 ((S)-(+)-6-(2-chlorophenyl)-3-cyclopropane-carbonyl-8,11-dimethyl-2,3,4, 5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2- f][1,2,4]triazolo[4,3-a][1,4]diazepine) (0.01, 0.1 and 1.0 mg/kg i.v.) and then exposed to 3 ppm ozone for 30 min. The PAF receptor antagonist significantly reduced the ozone-induced increase in microvascular leakage in a dose-dependent manner in both the trachea and main bronchi. Our results indicate that PAF mediates the ozone-induced increase in airway microvascular leakage. We therefore suggest that PAF may be involved in ozone-induced airway inflammation.
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PMID:Platelet-activating factor mediates the ozone-induced increase in airway microvascular leakage in guinea pigs. 779 63

1. The objectives of the present experiments were to assess the role of ETA receptors in mediating endothelin-1 (ET-1)-induced myocardial ischaemia and oedema and to study the involvement of platelet-activating factor (PAF) and thromboxane A2 (TxA2) in these actions of ET-1 in rats. 2. Intravenous bolus injection of ET-1 (0.1-2 nmol kg-1) into anaesthetized rats induced ST segment elevation of the electrocardiogram in a dose-dependent manner without causing arrhythmias. ST segment elevation developed within 20-90 s and persisted for at least 10-20 min following administration of ET-1. 3. Pretreatment of the animals with the selective endothelin ETA receptor antagonist, FR 139317 (2.5 mg kg-1, i.v.) inhibited by 86% the ST segment elevation elicited by ET-1 (1 nmol kg-1). Pretreatment with intravenous administration of BM 13505 (1 mg kg-1), a TxA2 receptor antagonist, OKY-046 (10 mg kg-1), a thromboxane synthase inhibitor or the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1) or BN 52021 (10 mg kg-1) markedly suppressed ST segment elevation in response to ET-1. Infusion of indomethacin (3 mg kg-1 bolus plus 2 mg kg-1 h-1) did not significantly affect ET-1-induced ST segment elevation. 4. Bolus injection of ET-1 (1 nmol kg-1, i.v.) to conscious rats resulted in a prolonged pressor effect preceded by a transient depressor response. Corresponding to changes in blood pressure, a small transient tachycardia was followed by a sustained bradycardia. ET-l enhanced albumin leakage by 87 and 120% in the left ventricle and right atrium, respectively, as measured by the extravasation of Evans blue dye.5. The selective ETA receptor antagonist, FR 139317 (2.5 mg kg-1) significantly blunted the pressor action of ET-1 and the accompanying bradycardia without affecting the depressor response. Furthermore,FR 139317 almost completely abolished the permeability effect of ET-l in both vascular beds studied.6. Pretreatment of the animals with BM 13505 (1 mg kg-1), OKY-046 (10mg kg-1), WEB 2086(1 mg kg-1) or BN 52021 (10mg kg-1) significantly reduced ET-1 (1 nmol kg-1)-induced albumin extravasation both in the left ventricle and right atrium. The PAF receptor antagonists, WEB 2086 and BN 52021 were equally potent inhibitors in the left ventricle, whereas BN 52021 appeared to be a more potent inhibitor than WEB 2086 in the right atrium. Pretreatment with indomethacin (3 mg kg-1 plus 2 mg kg-1 h-1) did not modify the permeability response to ET-1. None of these compounds affected significantly ET-l-induced changes in mean arterial blood pressure and heart rate.7. These results indicate that intravenous administration of ET-1 provokes ST segment elevation and myocardial oedema and suggest that these events are mediated, in part, through release of secondary mediators, such as PAF and TxA2 via the activation of ETA receptors.
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PMID:Endothelin-1-induced myocardial ischaemia and oedema in the rat: involvement of the ETA receptor, platelet-activating factor and thromboxane A2. 792 26

The effects of platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)-filled liposomes upon rat tracheal rings in vitro were examined. The capture of liposomes by the smooth muscle cells of the isolated tracheal rings as well as the release of their content into the cytoplasm was shown by using Evans blue (5 x 10(-4) M)-loaded liposomes. Administration of PAF (10(-3) M)-filled liposomes contracted the preparations, in contrast with extracellular administration of PAF and control liposomes, which had no effect. Administration during the plateau or pretreatment with liposomes containing BN 52021 (3-t-butylhexahydro-4,7b-trihydroxy-8-methyl-9H-1,7a-epoxymethano- 1H,6aH- cyclopenta[c]furo(2,3-b)furo[3',2':3,4]cyclopental [1,2-d]furan-5,9,12(4H)-trione) ((10(-3) M, a selective PAF receptor antagonist) or heparin (5 x 10(-5) M) blocked this contraction. BN 52021 and heparin, not entrapped in liposomes, had no such effect. Our data suggest an intervention of PAF in the mechanisms of contraction of tracheal smooth muscle, involving a direct or indirect intervention (intracellular receptors for PAF cannot be excluded). At the same time, the rat trachea contraction induced by PAF-loaded liposomes could be linked to the PtdIns(1,4,5)P3-dependent Ca2+ channels from the endoplasmic reticulum and/or to the interaction with G proteins, as shown by the blocking effects of heparin-containing liposomes.
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PMID:Effects of liposome-entrapped platelet-activating factor in the isolated rat trachea. 856 22

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.
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PMID:The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs. 905 14


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