Pharmacological characterization of SR 47436, a new nonpeptide AT1 subtype angiotensin II receptor antagonist.

SR 47436, 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one, is a new potent and selective AT1 angiotensin II (AII) receptor antagonist. It competitively inhibited [125I]AII binding to AT1 subtype receptors in rat liver membranes (IC50 = 1.7 nM) and did not interact with AT2 subtypes in rat adrenal cortical membranes.

SR 33557, a novel calcium-antagonist: interaction with [3H]-(+/-)-nitrendipine and [3H]-(-)-desmethoxy-verapamil binding sites in cerebral membranes.

We investigated the pharmacological properties of SR 33557, a novel compound with calcium-antagonist properties, in both functional tests in vitro and radioligand binding studies. SR 33557 potently antagonized calcium-induced contraction of potassium-depolarized rat aorta in vitro with an IC50 value of 5.6 +/- 0.

[Increase in plasma levels of active and inactive renin after inhibition of renin activity by SR 42128 in conscious Macaca monkeys].

Plasma active renin (PAR), plasma inactive renin (PIR), and plasma renin activity (PRA) were determined after intravenous bolus injection of the renin inhibitor SR 42128, in sodium repleted and sodium depleted macacas. The kit renin of Pasteur Diagnostics allows determination of PAR after renin inhibition by SR 42128. PAR and total plasmatic renin (TPR) were determined before and after treatment of plasma using trypsin.

A solid-phase radioimmunoassay using digitonin-permeabilized cells to screen surface or intracellular membrane-bound antigens.

Membrane-bound receptor or enzyme distribution between cell surface and cell interior can be determined using the non-ionic detergent digitonin. A solid-phase radioimmunoassay using myocardial cells from newborn rats was performed to screen hybridoma culture supernatants and the cells were rendered permeable with increasing concentrations of digitonin (0-0.1%).

Inhibition of platelet phospholipase-A2 as a mechanism for the anti-aggregating effect of linoleic acid.

Linoleic acid was incorporated into platelet phospholipids and then released after activation of phospholipase A2 (PL-A2) with thrombin or ionophore A23187. The rate of this release was tenfold lower for linoleic than for arachidonic acid. This observation strongly suggests that incorporation of linoleic acid in platelet phospholipids might inhibit platelet PL-A2 and might explain the anti-aggregating effect of linoelic acid.

Anti-inflammatory and platelet anti-aggregant activity of phospholipase-A2 inhibitors.

Mepacrine, papaverine, p-bromophenacyl bromide and 2,3-dibromo(4'-cyclohexyl-3'-chloro)-phenyl-4-oxo-butyric acid (CB 874) inhibit the hydrolysis of phospholipids induced by thrombin in dog platelets. They also exhibit anti-inflammatory and anti-aggregant properties. These biological activities may be explained by a direct or indirect inhibitory action on phospholipase A2.