RESUMO
A specific, high-affinity binding site for leukotriene C4 was identified in human erythrocyte particulate fraction and in vesicle preparation. The binding was saturable, reversible and specific. Vesicle preparations showed that binding sites were localized on the outside of the plasma membrane. The dissociation constant and site density were found to be Kd = 15.9 +/- 3.2 nmol X 1(-1) and N = 152 +/- 35 sites per cell, respectively, as calculated from Scatchard analysis. The effect of leukotriene C4 did not modify the calcium influx and did not inhibit the ATPase-dependent calcium efflux. In this paper, the physiological significance of these sites is discussed.
Assuntos
Eritrócitos/análise , Receptores de Prostaglandina/análise , Cálcio/metabolismo , Cálcio/farmacologia , Cromonas/farmacologia , Humanos , Leucócitos/análise , Receptores de Leucotrienos , TrítioRESUMO
PPARg (peroxisome proliferator-activated receptor gamma) is a nuclear receptor that regulates the transcription of numerous genes involved in the differentiation, proliferation and apoptosis of various cell types. It was initially discovered in adipocytes as a differentiation agent, then was characterized in vascular endothelium and recently in choroidal and retinal endothelial cells. Agonists that bind to PPARgamma and stimulate its transcriptional activity are endogenous lipids such as lysophosphatidic acid and 15-d-PGJ2 as well as the synthetic pharmacological compounds, thiazolidinediones, used for treating type 2 diabetes. These ligands prevent choroidal and retinal neovascularization in several experimental animal models, notably through the inhibition of vascular endothelial growth factor (VEGF) receptor expression. Because of the high affinity and the low molecular weight of agonists, suitable for good bioavailability, PPARgamma could potentially be a novel pharmacological target of angiostatic agents, particularly useful to treat age-related macular degeneration and diabetic retinopathy.
Assuntos
Neovascularização de Coroide/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , PPAR gama/uso terapêutico , Neovascularização Retiniana/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Apoptose , Células Cultivadas , Humanos , Ligantes , Peso Molecular , PPAR gama/genética , PPAR gama/metabolismo , PPAR gama/farmacologia , Polimorfismo Genético , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
The costovertebral organs [CVO] and seminel vesicles [SV] of the hamster exhibit high saturable androgen uptake. The physicochemcal characteristics of the cytoplasmic androgen receptor present in these tissues have been determined and compared to those obtained in rat prostate[P]. Using the synthetic androgen R 1881 [methyltrienolone] as a radioactive ligand, it has been shown that the affinity of this compound for the cytosol CVO receptor [Kd = 0.7 +/- 0.1 nM] is similar to that for the crytosol SV receptor [Kd = 2.4 +/- 0.9 nm] in hamsters and the cytosol P receptor [Kd = 0.6 +/- 0.1 nM] in rats. The hormonal specificity of binding in these tissues is restricted to androgens. Moreover, testosterone and dihydrotestosterone have the same relative binding affinity in CVO and SV compared to R 1881. Following castration, the total number of androgen sites, as measured by an exchange assay with R 1881, decreases rapidly and parallels with a fall in lipogenic activity. Administration of an androgen rapidly restores binding capacity.
Assuntos
Receptores Androgênicos/metabolismo , Receptores de Esteroides/metabolismo , Glândulas Sebáceas/metabolismo , Animais , Ligação Competitiva , Proteínas de Transporte/metabolismo , Castração , Cricetinae , Citosol/metabolismo , Di-Hidrotestosterona/metabolismo , Masculino , Glândulas Seminais/metabolismo , Testosterona/administração & dosagem , Testosterona/metabolismo , Congêneres da Testosterona/metabolismo , TrítioRESUMO
An in vitro model was designed to study the role of ischemia/reperfusion and oxygen free radicals on vascular prostacyclin (PGI2) synthesis and protection provided by superoxide dismutase (SOD). Cultured bovine aortic endothelial cells (BAEC) were subjected to various times of hypoxia (30 min to 5 h) followed by 30 min reoxygenation. An increase or a decrease in PGI2 synthesis capacity was then observed according to the duration of hypoxia. Inhibition of PGI2 synthesis after 5 h hypoxia/30 min reoxygenation was accompanied by a rise in lipoperoxidation products and a slight cytotoxicity. Superoxide anion could be implicated in these cellular alterations as SOD efficiently prevented these effects. Incubation of normoxic or H/R-treated BAEC with SOD led to an increase in cellular SOD activity as compared to controls. This increase, inhibited by incubation at 4 degrees C but not by addition of cycloheximide, strongly suggested endocytosis of SOD. This study emphasizes the role of endothelium as a source and target of free radicals and provides a new insight into the mechanism of protection by SOD in ischemia-related vascular pathology.
Assuntos
Endotélio Vascular/metabolismo , Epoprostenol/biossíntese , Hipóxia/metabolismo , Oxigênio/metabolismo , Superóxido Dismutase/farmacologia , Animais , Bovinos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Epoprostenol/antagonistas & inibidores , Sequestradores de Radicais Livres , Peroxidação de Lipídeos/efeitos dos fármacos , Oxigênio/farmacologia , Fatores de TempoRESUMO
Oxygen-derived free radicals are implicated in hypoxia- and reoxygenation-related brain injury. In addition, excitatory amino acid neurotransmitters seem to be involved in this neurotoxicity and could act through the L-arginine/nitric oxide (NO) synthase pathway. In the present study we have used rat forebrain neurons in culture submitted to hypoxia/reoxygenation to investigate the relative role of free radicals, glutamate, and nitric oxide in hypoxic neuronal injury. Hypoxia (5 h) followed by reoxygenation (0-24 h) induced cell damage assessed by lacticodehydrogenase release into culture medium. Superoxide dismutase (SOD, 500 U/mL), D-L-2-amino-5-phosphonovaleric acid (100 microM), a glutamate receptor antagonist, and NG-nitro-L-arginine (100 microM), an NO synthase inhibitor, protected the neurons. The effect of NG-nitro-L-arginine was reversed by adding L-arginine (10 mM) in the culture medium, and hemoglobin, which scavenges NO, also afforded protection. Hypoxia (5 h) provoked glutamate release from neurons, and this effect was inhibited by SOD. Exogenous glutamate (1-100 microM) induced lacticodehydrogenase release, and this effect was inhibited by glutamate antagonism, NO synthase inhibition, or superoxide radical scavenging. These data are consistent with the following sequence of events in hypoxia-related neurotoxicity: free radical formation, glutamate release, and activation of NO synthase leading to superoxide and NO cooperative toxicity.
Assuntos
Neurônios/efeitos dos fármacos , Óxido Nítrico/toxicidade , Superóxidos/toxicidade , Animais , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Hipóxia Celular , Células Cultivadas , Sinergismo Farmacológico , Radicais Livres , Glutamatos/metabolismo , Ácido Glutâmico , Neurônios/metabolismo , Ratos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismoRESUMO
An in vitro model was designed to study the role of ischemia/reperfusion and endothelium-derived oxygen free radicals on neutrophil adhesion, with particular interest in the endothelial adhesion molecules involved. Human umbilical vein endothelial cells were submitted to 5 h hypoxia followed by various times (20 min to 24 h) of reoxygenation. Human resting neutrophils were added to monolayers for the last 15 min of reoxygenation. Adherence was evaluated by myeloperoxidase assay. Under these conditions, we found an increased adhesion of neutrophils with two peaks after 20 min and 4 h reoxygenation. This was correlated with the respective expression of the preformed granule membrane protein 140 (GMP-140) and of the de novo synthesized endothelial leukocyte adhesion molecule 1 (ELAM-1) on endothelial surface. Superoxide dismutase and/or catalase, or oxypurinol added to cultures before hypoxia efficiently prevented neutrophil adhesion. These results underline the crucial role played by endothelial oxy radicals at reoxygenation in adhesion of leukocytes, which could lead to an amplification of the oxidative stress injury. The protection offered by free radical scavengers emphasizes the potential therapeutic use of antioxidants in postischemic vascular disorders.
Assuntos
Adesão Celular/fisiologia , Hipóxia Celular/fisiologia , Endotélio Vascular/fisiologia , Neutrófilos/fisiologia , Adulto , Moléculas de Adesão Celular/fisiologia , Células Cultivadas , Selectina E , Endotélio Vascular/citologia , Sequestradores de Radicais Livres , Radicais Livres , Humanos , Técnicas In Vitro , Neutrófilos/citologia , Oxigênio , Selectina-P , Glicoproteínas da Membrana de Plaquetas/fisiologiaRESUMO
A series of 1-hydroxy-3-¿3-hydroxy-7-phenyl-1-hepten-1-yl cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B(4) (LTB(4)) and evaluated as human cell surface LTB(4) receptor (BLTR) antagonists. Binding was determined through ¿(3)HLTB(4) displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB(4). On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3balpha (IC(50) = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5balpha, free of agonist activity, displayed higher potency in receptor binding with an IC(50) of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.
Assuntos
Cicloexanos/síntese química , Receptores do Leucotrieno B4/antagonistas & inibidores , Animais , Cicloexanos/química , Cicloexanos/farmacologia , Cobaias , Humanos , Leucotrieno B4/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ligação Proteica , Receptores do Leucotrieno B4/metabolismo , Espectrofotometria Infravermelho , Relação Estrutura-AtividadeRESUMO
We report the effects of CBS-211 A, a synthetic retinoic acid analog, on a previously described experimental model of keratoconjunctivitis sicca (KCS) in the rabbit. A 9-week topical treatment with 0.02% CBS-211 A in aqueous vehicle significantly increased the conjunctival goblet cell density (P less than 0.01, impression cytology counting), stopped the evolution of the corneo-conjunctival surface alteration (P less than 0.05, rose bengal test), and restored a basically normal mucosecretory product quality in goblet cells (lectin histochemistry) compared to vehicle treatment. The results assess the efficacy of this compound in reversing KCS pathology in a relevant model different from general vitamin A deficiency models, and strongly support the rationale for using such a well-tolerated retinoid in dry eye treatment.
Assuntos
Benzoatos/farmacologia , Ceratoconjuntivite Seca/tratamento farmacológico , Administração Tópica , Animais , Contagem de Células , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/ultraestrutura , Modelos Animais de Doenças , Ceratoconjuntivite Seca/patologia , Masculino , CoelhosRESUMO
CBS-1108, 2- acetylthiophene 2- thiazolyhydrazone , inhibits 5-lipoxygenase activity in polymorphonuclear leukocytes (PMNs) (IC50 = 2 X 10(-6) M), 12-lipoxygenase (IC50 = 9 X 10(-6) M) and cyclooxygenase (IC50 = 2 X 10(-6) M) in platelets. Inhibition of the two pathways of arachidonic acid cascade could lead to additional beneficial anti-inflammatory activity by comparison with classical aspirin-like drugs. In fact, only inhibitors of both cyclooxygenase and lipoxygenase such as NDGA and CBS-1108 inhibit leukocyte migration in an animal model of acute inflammatory response.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase , Inibidores de Lipoxigenase , Tiazóis/farmacologia , Animais , Araquidonato Lipoxigenases , Aspirina/farmacologia , Plaquetas/enzimologia , Carboximetilcelulose Sódica/farmacologia , Humanos , Inflamação/sangue , Masculino , Neutrófilos/enzimologia , Coelhos , Ratos , Ratos EndogâmicosRESUMO
We have studied the effects of KUM 32 and CBS 1276, two clonidine-related drugs, upon the adenylate cyclase system of human platelets. Both drugs behaved as potent antagonists of epinephrine-induced platelet aggregation. [3H]Yohimbine binding studies revealed that the drugs bind to the alpha 2 adrenergic receptor of human platelets. KUM 32 and CBS 1276 also behaved as strong inhibitors of adenylate cyclase activity. This inhibition, which was not competitive with respect to ATP, is not an alpha 2 adrenergic phenomenon since it was not antagonized by yohimbine and was still observed in the absence of GTP. Moreover, pretreatment of platelet membranes with islet activating protein from Bordetella pertussis (IAP) had no effect on the inhibition by KUM 32, CBS 1276 and adenosine, although it completely reversed the effect of epinephrine and partially reversed the effect of clonidine. These results show that clonidine-like drugs may have different impacts on the adenylate cyclase system of human platelets. This system cannot be used as a pharmacological predictive test for alpha 2 adrenergic agonist activity, as various compounds, known to have central alpha 2 adrenergic agonist properties, do not behave as full agonists for the alpha 2 adrenergic receptor of human platelets.
Assuntos
Inibidores de Adenilil Ciclases , Plaquetas/enzimologia , Clonidina/análogos & derivados , Receptores Adrenérgicos alfa/efeitos dos fármacos , Toxina Adenilato Ciclase , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Clonidina/metabolismo , Clonidina/farmacologia , Humanos , Cinética , Toxina Pertussis , Agregação Plaquetária/efeitos dos fármacos , Fatores de Virulência de Bordetella/farmacologia , Ioimbina/metabolismoRESUMO
The growing evidence that glutamate may be an important agent mediating ischemic damage to neurons, led us to investigate the possible protective effects of pharmacological agents against glutamate in a model system of cortical neurons. In this study we examined, in particular, the cytoprotective effect of prostaglandins. Experiments were carried out in vitro by using rat cortical neurons in culture for 10 days. They were incubated for 3h with glutamate (10 microM) in the presence or absence of various pharmacological agents including prostaglandins (PGD2, PGE1, PGE2, PGF2 alpha, PGI2, 6-Keto-PGF1 alpha, carba-TXA2, carba-PGI2 and PGF2 alpha-methylester). Increase in lacticodehydrogenase (LDH) release into the culture medium has been measured as an index of cell injury. When neurons were incubated with glutamate they released LDH due to NMDA-receptor activation since D-L-2-amino-5-phosphonovaleric acid, a specific receptor antagonist, protected the cells. The protective activity of oxypurinol, amflutizole, superoxide dismutase, NG nitro-L-arginine and quinacrine, also suggests that xanthine oxidase activation, the generation of superoxide radical, and nitrix oxide, as well as phospholipase A2 stimulation are responsible for neuron injury (i.e. LDH release). All the tested prostaglandins, except PGF2 alpha-methylester, afforded significant protection at concentrations between 0.1 and 10 microM. The order of potency of the prostanoids was: PGF2 alpha = PGE2 > Carba-TXA2 > PGE1 > PGD2 > PGI2 = Carba-PGI2 > 6-Keto-PGF1 alpha. Additional experiments showed that prostaglandins did not compete for the NMDA binding site and that they did not inhibit free radical-related membrane damage.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Córtex Cerebral/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios , Neurônios/efeitos dos fármacos , Neurotransmissores/antagonistas & inibidores , Prostaglandinas/farmacologia , Animais , Células Cultivadas , Córtex Cerebral/citologia , Glutamatos/toxicidade , Ácido Glutâmico , Neurotransmissores/toxicidade , RatosRESUMO
Arachidonic acid and its metabolites are released in brain extracellular fluids as a result of ischemia and may participate in either damaging or protecting neural tissues. This study investigates the neuroprotective effect of prostacyclin (PGI2) on hypoxia (5 h)/reoxygenation (3 h) and on the excitotoxic neurotransmitter, glutamate (10 microM), in rat cortical neuron cultures. At microM concentrations, PGI2 inhibits lactate dehydrogenase release, a cell-injury marker. These results, showing a direct cytoprotective effect of PGI2 on brain cells, reinforce its beneficial properties on vessels and circulating cells in cerebral ischemia.
Assuntos
Córtex Cerebral/citologia , Epoprostenol/farmacologia , Antagonistas de Aminoácidos Excitatórios , Hipóxia Encefálica/patologia , Neurônios/efeitos dos fármacos , Oxigênio/antagonistas & inibidores , 6-Cetoprostaglandina F1 alfa/farmacologia , Animais , Células Cultivadas , Córtex Cerebral/enzimologia , Feminino , Glutamatos/toxicidade , Ácido Glutâmico , L-Lactato Desidrogenase/metabolismo , Neurônios/enzimologia , Oxigênio/toxicidade , Gravidez , RatosRESUMO
Cultured rat retinal neurons exposed to kainate produced free radicals, as demonstrated by electron spin resonance (ESR) spin trapping using the nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and the generation of DMPO hydroxyl adduct (DMPO-OH). This DMPO-OH production was abolished by EGTA, nitro-arginine and oxypurinol, suggesting that it was dependent on Ca2+ influx and subsequent activation of nitric oxide synthase and xanthine oxidase. Moreover, kainate induced a receptor-mediated Ca2+ influx and neuronal injury assessed by lactate dehydrogenase release. Neuroprotection afforded by nitro-arginine and oxypurinol shows that calcium-dependent free radical production plays a major role in kainate retinal toxicity.
Assuntos
Cálcio/fisiologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Radicais Livres/metabolismo , Ácido Caínico/toxicidade , Neurônios/metabolismo , Retina/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Células Cultivadas , Espectroscopia de Ressonância de Spin Eletrônica , L-Lactato Desidrogenase/metabolismo , Neurônios/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina , Oxipurinol/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Retina/citologia , Retina/efeitos dos fármacos , Xantina Oxidase/antagonistas & inibidoresRESUMO
Methyltrienolone (R 1881), 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one, a very active androgen, binds specifically to rat prostate cytosol with a higher affinity than androstanolone. Unlike the physiological hormone, however, it is not bound by human sex steroid plasma binding protein, SBP. This specific ligand is thus a useful tool for the detection of elusive androgen receptors and for their study, for instance, in human tumors where interference from plasma contamination has to be circumvented.
Assuntos
Estrenos/metabolismo , Receptores de Superfície Celular , Congêneres da Testosterona/metabolismo , Animais , Ligação Competitiva , Proteínas Sanguíneas/metabolismo , Citosol/metabolismo , Di-Hidrotestosterona/metabolismo , Humanos , Cinética , Masculino , Próstata/metabolismo , Ligação Proteica , RatosRESUMO
Methyltrienolone (R 1881 - 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) binds specifically to androgen receptor in rat prostate cytosol where, unlike androstanolone, it is not metabolized. By exchanging bound endogenous hormone in rat prostate cytosol with labelled R 1881, it is possible to measure total (free anc occupied) binding sites. This assay method has also been applied to the measurement of androgen receptor sites in human benign prostatic hypertrophy where R 1881 has the added advantage of not being bound by any contaminating plasma protein (sex hormone binding protein).
Assuntos
Di-Hidrotestosterona/metabolismo , Estrenos/metabolismo , Receptores de Superfície Celular , Congêneres da Testosterona/metabolismo , Animais , Citosol/metabolismo , Humanos , Masculino , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Ligação Proteica , Ratos , TemperaturaRESUMO
Methyltrienolone (R 1881 - 17beta-hydroxy-17alpha-methyl-estra-4, 9, 11-trien-3-one) binding to rat ventral prostate cytosol has a specificity typical of an androgen receptor. In human benign prostatic hypertrophy (BPH) tissue, the specificity of [3H] R 1881 binding is different from that measured in rat prostate: progesterone and R 5020 (17, 21-dimethyl-19-nor-4, 9-pregnadiene-3, 20-dione) being more potent while 19-nortestosterone is less potent competitor. Moreover, the synthetic progestin [3H] R 5020 binds to BPH tissue with a similar specificity. These data suggest the presence of progestin binding components or of an atypical androgen receptor in human BPH cytosol.
Assuntos
Estrenos/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Congêneres da Testosterona/metabolismo , Animais , Ligação Competitiva , Citosol/metabolismo , Feminino , Humanos , Cinética , Masculino , Progesterona/metabolismo , Ratos , Receptores Androgênicos/metabolismo , Receptores de Progesterona/metabolismo , Útero/metabolismoRESUMO
Epidermal growth factor (EGF) is mitogenic for bovine corneal endothelial cells in culture. Pretreatment with either retinoic acid or the synthetic analog CBS-211 A ((E)-4-[2-(2-isopropyl-5-thienyl)propenyl]benzoic acid) at 10(-8)-10(-6) M enhanced the EGF effect. This potentiating effect of retinoids contrasts with their intrinsic activity, which results in cell growth inhibition in the absence of growth factor. The present data emphasize the previously reported beneficial effect of retinoic acid on corneal endothelium wound healing. This effect could be related to the potentiation of endogenous growth factors and further underlines the importance of retinoids in the medical treatment of corneal endothelial lesions.
Assuntos
Endotélio Corneano/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , Mitógenos/farmacologia , Tretinoína/farmacologia , Animais , Benzoatos/farmacologia , Bovinos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Sinergismo Farmacológico , Endotélio Corneano/citologiaRESUMO
Erythrocyte deformability and aggregability, fibrinogen plasma level, and hematocrit were measured in patients with primary open-angle glaucoma and in age-matched control subjects. Only one parameter, red blood cell rigidity, as evaluated by the Hanss filtration technique, was found significantly elevated in glaucoma patients. This erythrocyte abnormality, which corroborates previous data on blood viscosity, could be an important factor in the pathogenesis of optic nerve damage and could support the hypothesis of a primary oxidative stress in glaucoma.
RESUMO
An experimental model of optic nerve ischemia was designed in the rabbit to determine early biochemical alterations, i.e.--changes of high energy phosphate metabolites (ATP and phosphocreatine)--in occlusive and peri-occlusive areas. Vascular occlusion provoked a rapid fall of ATP and phosphocreatine in the optic nerve. Free radicals scavengers, superoxide dismutase plus catalase or dimethylthiourea were able to counteract the drop of phosphate metabolites in the peri-occlusive area. These results show that hypoxia leads to oxygen-derived free radical generation which can be responsible for cell damage and emphasize the role of free radicals in the pathogenesis of ocular diseases related to vascular dysfunction.
Assuntos
Trifosfato de Adenosina/metabolismo , Isquemia/metabolismo , Nervo Óptico/irrigação sanguínea , Fosfocreatina/metabolismo , Animais , Catalase , Modelos Animais de Doenças , Sequestradores de Radicais Livres , Radicais Livres , Consumo de Oxigênio , Coelhos , Superóxido Dismutase , Tioureia/análogos & derivadosRESUMO
Anterior chamber paracentesis of the rabbit eye causes disruption of the blood-aqueous barrier, which is characterized by a rapid increase in the albumin and total protein content of the aqueous humor. Prostaglandins appear to be implicated as major mediators in this reaction, since a cyclooxygenase inhibitor, indomethacin, very efficiently prevents protein leakage. When paracentesis was performed in platelet-depleted rabbits (either by transfusion or by treatment with an antiplatelet plasma), the protein content in the aqueous humor did not rise to values observed in normal animals. These data suggest that platelets play some role in the response to paracentesis, a fact in accordance with histological results. In contrast to cyclooxygenase inhibitors, dexamethasone inhibits neither the blood-aqueous barrier breakdown nor prostanoid release from platelets. These data also indirectly indicate the possible role of platelets in triggering the paracentesis reaction in the rabbit.