G J Blackwell

Bio: G J Blackwell is an academic researcher. The author has contributed to research in topics: Prostaglandin E2 receptor & Mechanism of action. The author has an hindex of 1, co-authored 1 publications receiving 873 citations.

Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation.

Abstract: ASPIRIN prevents prostaglandin (PG) generation by directly inhibiting the cyclo-oxygenase enzyme responsible for PG biosynthesis1–3. In addition, there is now conclusive evidence that anti-inflammatory steroids can also prevent PG generation4–13. Unlike the aspirin-like drugs, steroids have no anti-cyclo-oxygenase activity but exert their action by preventing the release from phospholipids of the fatty acid substrates required for PG biosynthesis4–9,12,13. We have shown that stimulation of thromboxane A2 (TXA2) release by agents such as histamine, 5-hydroxytryptamine and rabbit aorta contracting substance-releasing factor (RCS–RF) (but not arachidonic acid) is inhibited by anti-inflammatory steroids, and that their potency in this action closely parallels their anti-inflammatory activity12,13. Furthermore, their mechanism of action involves the inhibition of phospholipase A2 activity, and thus of arachidonate release within the lung12,13. In several other tissues, the mechanism of steroid hormone action depends on the combination of thesteroid with a cytosolic receptor protein, the translocation of this drug–receptor complex to the nucleus and the initiation of protein biosynthesis14–16. We now show that similar events occur in the guinea pig perfused lung before inhibition by steroids of phospholipase A2 activity (and thus TXA2 generation). We have discovered a steroid-induced factor which mimics the anti-phospholipase effects of these anti-inflammatory agents.

Regulatory functions of the vascular endothelium.

Abstract: William harvey, when studying the circulation of the blood, must have recognized that "In sound and living vessels the blood remains fluid, but it coagulates in dead ones" (Ernst Brucke, 1857). Joseph Lister (1909) provided further evidence for an active role of blood vessels in maintaining the liquidity of blood. The vascular endothelium, which envelops the circulating blood in a continuous monolayer, is mainly responsible for this function. Over the past 20 years numerous other important functions have been discovered. For instance, the outer surface of the endothelial cell contains angiotensin-converting enzyme, which catalyzes the formation of the vasoconstrictor angiotensin . . .

How is the level of free arachidonic acid controlled in mammalian cells

Abstract: Over the last 25 years a considerable research effort has concentrated on the eicosanoids, and great progress has been made in the elucidation of the chemical structure of these compounds, of their physiological roles, and of the ways in which their synthesis is controlled. It is on the last of these that this Review will concentrate, for it is now established that in most tissues the synthesis of eicosanoids is limited by the availability of their common precursor, free arachidonic acid, which must be liberated from esterified stores in complex lipids (van Dorp et al., 1964; Bergstrom et al., 1964; Vogt et al., 1966; Lands & Samuelsson, 1968; Vonkeman & van Dorp, 1968). Control of the subsequent metabolism of the free acid will not be discussed here, nor will the original derivation of arachidonate from dietary sources (reviewed by Willis, 1981). The purposes of this Review are twofold: firstly, it is useful to summarize briefly the present state of knowledge in order to help newcomers in the field; secondly, and more importantly, in order to move forward both conceptually and experimentally it is necessary to take a critical look at the complexities and problems associated with studying arachidonate liberation. Liberation of arachidonate, as defined here, must involve hydrolysis of an ester bond i.e. lipase activity. The three essential questions concerning the control of arachidonate availability are therefore: (1) Which lipases are involved? (2) How are they controlled? (3) Which substrates are hydrolysed?