Role Of Chondroitin 4-sulphate As A Receptor For Polycation Induced Human Platelet Aggregation.

dc.creatorDonato, J L
dc.creatorMarcondes, S
dc.creatorAntunes, E
dc.creatorNogueira, M D
dc.creatorNader, H B
dc.creatorDietrich, C P
dc.creatorRendu, F
dc.creatorde Nucci, G
dc.date1996-Dec
dc.date2015-11-27T12:18:49Z
dc.date2015-11-27T12:18:49Z
dc.date.accessioned2018-03-29T00:51:58Z
dc.date.available2018-03-29T00:51:58Z
dc.identifierBritish Journal Of Pharmacology. v. 119, n. 7, p. 1447-53, 1996-Dec.
dc.identifier0007-1188
dc.identifier
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/8968554
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/193961
dc.identifier8968554
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1294194
dc.description1. Proteoglycans provide negatively charged sites on the surface of platelets, leukocytes and endothelial cells. Since chondroitin 4-sulphate is the main proteoglycan present on the platelet surface, the role of this molecule in mediating the activation of human platelets by polylysine was studied. 2. Platelets were desensitized with phorbol 12-myristate 13-acetate (PMA, 10 nM) 5 min before the addition of polylysine to platelet-rich plasma (PRP). Changes in the intracellular Ca2+ concentration were measured in fura2-am (2 microM) loaded platelets and protein phosphorylation was assessed by autoradiography of the electrophoretic profile obtained from [32P]-phosphate labelled platelets. The release of dense granule contents was measured in [14C]-5-hydroxytryptamine loaded platelets and the synthesis of thromboxane (TXA2) was assessed by radioimmunoassay. Surface chondroitin 4-sulphate proteoglycan was degraded by incubating platelets with different concentrations of chondroitinase AC (3 min, 37 degrees C). The amount of chondroitin 4-sulphate remaining in the platelets was then quantified after proteolysis and agarose gel electrophoresis. 3. The addition of PMA to PRP before polylysine inhibited the aggregation by 88 +/- 18% (n = 3). Staurosporine (1 microM, 5 min) prevented the PMA-induced inhibition. Chondroitinase AC (4 pu ml-1 to 400 muu ml-1, 3 min) abolished the polylysine-induced aggregation in PRP but caused only a discrete inhibition of ADP-induced aggregation. The concentration of chrondroitin 4-sulphate in PRP (0.96 +/- 0.2 microgram/10(8) platelets, n = 3) and in washed platelets (WP; 0.35 +/- 0.1 microgram/10(8) platelets, n = 3) was significantly reduced following incubation with chondroitinase AC (PRP = 0.63 +/- 0.1 microgram/10(8) platelets and WP = 0.08 +/- 0.06 microgram/10(8) platelets). 4. Washed platelets had a significantly lower concentration of chondroitin 4-sulphate than platelets in PRP. The addition of polylysine to WP induced a rapid increase in light transmission which was not accompanied by TXA2 synthesis or the release of dense granule contents. This effect was not inhibited by sodium nitroprusside (SNP), iloprost, EDTA or the peptide RGDS. This event was accompanied by the discrete phosphorylation of plekstrin and myosin light chain, which were inhibited by staurosporine (10 microM, 10 min). The hydrolysis of platelet surface chondroitin 4-sulphate strongly reduced the polylysine-induced phosphorylation. 5. Our results indicate that polylysine activates platelets through a specific receptor which could be the proteoglycan chondroitin 4-sulphate present on the platelet membrane.
dc.description119
dc.description1447-53
dc.languageeng
dc.relationBritish Journal Of Pharmacology
dc.relationBr. J. Pharmacol.
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectBlood Platelets
dc.subjectBlood Proteins
dc.subjectCalcium
dc.subjectChondroitin Sulfates
dc.subjectEosinophils
dc.subjectGlycosaminoglycans
dc.subjectHumans
dc.subjectIn Vitro Techniques
dc.subjectPhosphorylation
dc.subjectPlatelet Aggregation
dc.subjectPlatelet Aggregation Inhibitors
dc.subjectPolylysine
dc.subjectSerotonin
dc.subjectThromboxane A2
dc.titleRole Of Chondroitin 4-sulphate As A Receptor For Polycation Induced Human Platelet Aggregation.
dc.typeArtículos de revistas


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