Rosemary Murray

Induction of prostacyclin receptor expression in human erythroleukemia cells

We have identified both high‐affinity (KD = 36±3 nM) and low‐affinity (KD = 2.1±0.8 μM) prostacyclin (PGI2)‐receptor sites on human erythroleukemia (HEL) cells using the radiolabelled prostacyclin analogue, [3H]iloprost. The addition of the phorbol ester, TPA, to the culture medium caused a 5–10‐fold increase in the number of both the low‐ and the high‐affinity sites, without any change in their affinity constants. Iloprost stimulated HEL cell membrane adenylate cyclase activity 5‐fold. This stimulation was potentiated in the presence of GTP, indicating a conventional PGI2 receptor‐Gs‐adenylate cyclase system. HEL cells represent a source of prostacyclin receptor mRNA which may be of value in expression cloning of this receptor.

The Molecular, Biochemical and Human Pharmacology of Thromboxane A2 in Renal Disease

Arachidonic acid is a constituent of the phospholipid domain of biological membranes. Activation of phospholipases results in its release into the intracellular milieu where it is subject to metabolism to biologically active compounds. In most cell types, including the platelet (1), the predominant enzyme involved in catalyzing arachidonate release is phospholipase A2 rather than phospholipase C (2). It has recently been shown that arachidonate may be subject to direct oxygenation within the cell membrane (3); the biological role of this process remains speculative.

Synthesis of a fluorescent labeled thromboxane A2 receptor antagonist

Abstract The synthesis and biological evaluation of a fluorescent labeled probe for the thromboxane A 2 receptor is described.

Thromboxane A2 synthesis in pregnancy-induced hypertension

Urinary excretion of thromboxane B2 metabolites as markers of thromboxane A2 synthesis was measured in eight patients with moderate to severe pregnancy-induced hypertension and in six normotensive pregnant women at term. Excretion of both 2,3-dinor-TxB2 (median 3919, range 683-16,680 pg/mg creatinine) and 11-dehydro-TxB2 (median 10,187, range 434-57,203 pg/mg creatinine) was significantly higher in the patients with pregnancy-induced hypertension than in the normotensive pregnant group (927[273-1343] and 774[500-2760] pg/mg creatinine, respectively). Thromboxane metabolite excretion correlated with mean arterial blood pressure, plasma lactate dehydrogenase, and platelet count which are indices of the severity of pregnancy-induced hypertension. Excretion of both metabolites fell rapidly post partum in parallel with resolution of clinical signs. Thus, increased thromboxane A2 biosynthesis correlates with disease severity and may have a pathogenetic role in pregnancy-induced hypertension. These findings provide a rationale for the use of aspirin in the treatment as well as in the prevention of this disorder.