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Biomedical subjects

A M Shaw

Publications and source records attributed to A M Shaw.

24 records · Page 2Linked to original sources
PubMed1985

Endogenous and pharmacological mechanisms for the regulation of human platelet cytosolic free Ca2+.

Because they inhibit the processes that promote elevation of [Ca2+]i and augment the processes that promote removal of Ca2+ from the cytosol, receptor antagonists, agents that mimic or elevate cAMP, cGMP or 1,2-Diacylglycerol (DG), and both inorganic and organic Ca2+ channel blockers can be considered to act as 'Ca2+ antagonists' on human platelets. Agonist-induced elevation of [Ca2+]i is associated with phosphoinositide hydrolysis. Unlike agents that mimic or elevate cAMP, cGMP or DG, receptor antagonists and organic Ca2+ influx, mobilisation of internal Ca2+ and inositol lipid hydrolysis. Lanthanides apparently inhibit only Ca2+ influx. Thus La3+ but not Verapamil or Diltiazem block receptor-operated Ca2+ channels on human platelets. The endogenous processes that promote extrusion or sequestration of cytosolic Ca2+ may be augmented by cAMP, cGMP, DG and by Ca2+. DG, via activation of protein kinase C, may serve as a bi-directional regulator of platelet reactivity.

Aminoquinolines↗
PubMed1983

Phospholipid-induced human platelet activation: effects of calcium channel blockers and calcium chelators.

Human platelet activation (aggregation, [14C]-5HT release and TxB2 production) induced by the phospholipids, PAF and lysophosphatidic acid (LPA) was inhibited by EGTA, TMB-8 (an intracellular calcium antagonist) and by phenylalkylamine (Class II) but not 1,4-dihydropyridine (Class I) calcium channel blockers. Primary aggregation induced by PAF was selectively inhibited by phenylalkylamine (verapamil, methoxyverapamil) calcium channel blockers. Phospholipid-induced human platelet activation depends predominantly on the influx of extracellular calcium, possibly via specific receptor-operated calcium channels.

Biological Transport↗
PubMedDate not supplied

Platelet activation--a role for a 40K anti-phospholipase A2 protein indistinguishable from lipocortin.

Stimulus-response (S-R) coupling in platelets requires an intermediary other than an elevation in cytosolic free calcium ([Ca2+]i). While an increase in [Ca2+]i is essential in S-R coupling, effecting phosphorylation of myosin of relative molecular mass (Mr) 20,000 (20 K), platelet activation is also associated with phosphorylation of a 40K protein, which can occur in the absence of changes in [Ca2+]i. The 40K protein is the substrate for protein kinase C (PKC). Mounting evidence suggests that activation of PKC by diacylglycerol is the other signal involved in S-R coupling. Although phosphorylation of the 40K protein is associated with certain platelet functional responses, no precise role has been accredited to it. Recently, we and others have described several proteins (collectively known as lipocortin) which inhibit phospholipase A2 (PLA2). One of the most conspicuous proteins of this group is a 40K peptide whose inhibitory activity can be suppressed by prior phosphorylation. We hypothesized that the 40K protein described in platelets may possess anti-PLA2 activity and that phosphorylation by PKC, suppressing its inhibitory activity, may represent the mechanism underlying mobilization of arachidonic acid, the precursor of prostaglandins. The results of the present study strongly support this hypothesis.

Alkaline Phosphatase↗