Gill, Jasvinder Kaur; (1994) Calcium uptake by platelets in relation to the aetiology and treatment of vascular disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Some aspects of calcium (45Ca2+) uptake by isolated washed human and rat platelets in relation to intracellular second messengers, cardiovascular disease and drug action was studied. It was first established that both α - and β- adrenoceptor agonists (activators and inhibitors of platelet function, respectively) elicit the uptake of 45Ca2+. Subsequent studies demonstrated that this uptake of 45Ca2+ may reflect local changes of Ca2+ at the plasma membrane and signal transduction mechanisms (G protein and protein kinase A and C activation). These findings extended to other stimulators (collagen, adenosine diphosphate, Ca2+ ionophore A23187) and inhibitors (dibutyryl cyclic adenosine 3'5'-monophosphate and iloprost [a prostacyclin analogue]) of platelet function. In studies on drug action, it was found that inhibitors of platelet function (angiotensin converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, Ca2+ channel blocking drugs) also inhibit the uptake of 45Ca2+, suggesting that their mode of action also involves the inhibition of Ca2+ mobilisation. 45Ca2+ uptake in platelets from patients in which platelet hyperaggregabi1ity has been reported (anorexia nervosa [AN], peripheral vascular disease [PVD], diabetes mellitus [DM]) was studied. In AN,α- and β-adrenoceptor-stimulated 45Ca2+ uptake was increased and decreased, respectively. In platelets from patients with type I and type II DM, basal 45Ca2+ uptake was significantly enhanced. In contrast, agonist-stimulated 45Ca2+ uptake was significantly diminished in type I DM. In type II diabetics, α- and β-adrenoceptor-stimulated 45Ca2+ uptake was enhanced. In PVD patients, agonist-stimulated 45Ca2+ uptake by platelets was unaltered. Studies on platelets from diabetic rats revealed that α- and β-adrenoceptor-stimulated 45Ca2+ uptake was increased and decreased, respectively. It is concluded that in conditions associated with platelet dysfunction, there are marked alterations in Ca2+ sequestration at the plasma membrane level. The relevance of these findings is discussed in relation to previous reports of altered platelet function in these conditions.

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