ACTIVATION OF BLOOD-PLATELETS
| dc.contributor.author | JAMALUDDIN, M | |
| dc.date.accessioned | 2017-03-10T03:25:20Z | |
| dc.date.available | 2017-03-10T03:25:20Z | |
| dc.date.issued | 1993 | |
| dc.description.abstract | Platelets are small anucleate and excitable blood cells derived from megakaryocytes of bone marrow. Their activation by various exogenous stimuli that are exposed and engendered in vascular exigencies, plays crucial roles in haemostasis and thrombosis and is implicated in various other cardiovascular diseases. Molecular mechanisms of cause-effect relationships are not yet clearly understood but evidence for stimulus (agonist)-directed, receptor-operated, sequential activation of two major interacting biochemical pathways for activation of protein kinase C (PKC) has accumulated. One of these is linked to phospholipase C (PLC) activation and the other to phospholipase A2 (PLA2) activation and formation of cyclo-oxygenase products. These pathways provide mechanisms for the transformation of the plasma-membrane glycoprotein IIb-IIIa, the platelet-specific integrin, into an aggregation-competent form and regulation of platelet activation. Our understanding of the aggregation reaction is rudimentary. Contrary to common belief a first order rate law seems to apply. The author has proposed a sequential shape-change and interaction model of aggregation. On its basis a rate equation for platelet aggregation was derived. A spectrophotometric method of following shape-change reactions of platelets and quantitating single-platelet recruitment into aggregates has also been devised. The results of their application to the aggregation of gel-filtered calf platelets can be summarized as follows: Epinephrine did not aggregate but inhibited the aggregation induced by ADP. U-46619 and collagen induced only shape-change no aggregation but enhanced the aggregation by ADP. The kinetics of ADP-and phorbol myristate acetate (PMA)-induced aggregation showed apparent hyperbolic pattern (linear double-reciprocal plots and h=1). The kinetics of aggregation by thrombin, A 23187, Paf, arachidonic acid and H2O2 showed apparent positive co-operativity ('concave up double-reciprocal plots and h > 1). Paf has the lowest and H2O2 the highest half-maximal saturation concentrations. PMA showed the lowest and H2O2 the highest maximum rates. Arachidonate and H2O2 were found to be ligands for a dimeric haemoprotein (Mr approximately 40,000) purified from calf platelets. These ligands as well as the PGH2/TxA2 analogue U-46619 induced conformational changes in the purified protein. Similar conformational changes were found in the protein in intact platelets upon their activation. Ligand-induced conformational change of the protein has been proposed as a mechanism of platelet activation. H2O2 activates platelets by acting at two different sites one of which is the putative PGH2/TxA2 receptor, possibly its SH group(s). Adenosine and ATP have been found to be mutually exclusive modifiers of the kinetics of ADP-induced aggregation. | |
| dc.identifier.citation | 52 ,2;68-80 | en_US |
| dc.identifier.uri | https://dspace.sctimst.ac.in/handle/123456789/9234 | |
| dc.publisher | JOURNAL OF SCIENTIFIC & INDUSTRIAL RESEARCH | |
| dc.subject | Engineering | |
| dc.title | ACTIVATION OF BLOOD-PLATELETS |