Cyclic AMP and platelet prostaglandin synthesis

Gerrard, Jonathan M.; Peller, Janet D.; Krick, Thomas P.; White, James G.

doi:10.1016/0090-6980(77)90155-1

Cited by 93 publications

(21 citation statements)

References 8 publications

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“…PGD2 does not appear to achieve this general inhibition by depressing cyclooxygenase activity, since the response of aspirin-treated d0 platelets to collagen is inhibited 90% by PGD2. The (32)(33)(34). The PI response in thrombin-stimulated platelets (which is not dependent on cyclooxygenase activity) is also inhibited by cAMP (7).…”

Section: Resultsmentioning

confidence: 99%

Synergistic activation by collagen and 15-hydroxy-9 alpha,11 alpha-peroxidoprosta-5,13-dienoic acid (PGH2) of phosphatidylinositol metabolism and arachidonic acid release in human platelets.

Rittenhouse¹,

Allen²

1982

J. Clin. Invest.

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A B S T R A CT Collagen stimulates the activation of phosphatidylinositol (PI)-specific phospholipase C (EC 3.1.4.10) in human platelets, as manifested by the disappearance of PI, the transient formation of diacylglycerol (DG), and release of myoinositol. Platelets exposed to collagen also form lysophosphatidylinositol (LPI). Maximum formation of DG occurs within 60 s of the addition of collagen and is in proportion to the concentration of collagen provided, up to 100 Mg!2 X 109 platelets/ml. Hydrolysis of PI, formation of DG, and release of arachidonic acid are all inhibited -68% by aspirin or indomethacin, both of which inhibit platelet cyclooxygenase. This inhibition is reversed by the product of cyclooxygenase activity, 15-hydroxy -9a,lla -peroxidoprosta -5,13 -dienoic acid (PGH2), or by the PGH2 analogue and agonist, U-46619. The counteracting effects of either PGH2 or the PGH2 analogue can be blocked, in turn, by a PGH2 antagonist, U-51605. Neither PGH2 nor its stable analogue is, by itself, an efficient stimulus for PI breakdown to DG and LPI in platelets. However, in conjunction with collagen, these agents synergistically promote the net breakdown of PI and the release of arachidonic acid in aspirin-treated platelets. Our findings thereby imply that PGH2 has an important role in regulating both the release of its precursor, arachidonic acid, and the metabolism of PI induced by collagen.Dibutyryl cyclic AMP or prostaglandin D2 (PGD2), a prostaglandin that elevates concentrations of cAMP in platelets by stimulating adenylate cyclase, inhibits the hydrolysis of PI induced by collagen by 70%. The activation of PI metabolism by collagen appears to be

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Section: Resultsmentioning

confidence: 99%

Synergistic activation by collagen and 15-hydroxy-9 alpha,11 alpha-peroxidoprosta-5,13-dienoic acid (PGH2) of phosphatidylinositol metabolism and arachidonic acid release in human platelets.

Rittenhouse¹,

Allen²

1982

J. Clin. Invest.

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“…Free fatty acid levels are very low in most tissues, and phospholipase activation is believed to be required for prostaglandin biosyn- thesis (1,5,16,(19)(20)(21)(22). This activation can be brought about in different tissues through a variety of stimuli, such as bradykinin, angiotensin II, vasopressin, thrombin, collagen, serum, ionophore A23187, and trypsin (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(19)(20)(21)(22).…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, thrombin, collagen, ionophore A23187, or trypsin causes a very rapid and marked activation of platelet phospholipase A2 activity (2-13). The released arachidonate is then metabolized through the two known pathways which involve cyclooxygenase and lipoxygenase activities (2,3,11). Activation of phospholipase A2 activity can be prevented by adenosine 3':5'-cyclic monophosphate (cAMP) (4)(5)(6)(10)(11)(12).…”

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confidence: 99%

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Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets

Lapetina

Cuatrecasas

1979

Proc. Natl. Acad. Sci. U.S.A.

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Try sin, thrombin, and ionophore A23187 activate phospholipid breakdown of conditions that lead to use of the latter also results in a similarly rapid inhibition of cyclooxygenase activity, as determined by subsequent challenge with thrombin. Under these conditions lipoxygenase activity is much less markedly inactivated. The arachidonate-induced inhibition of cyclooxygenase activity is not prevented by cyclic AMP. Trypsin does not induce platelet aggregation, and platelets whose cyclooxygenase activity has been inactivated are intact insofar as they are still able to undergo aggregation. These studies demonstrate that operation in intact platelets of the cyclooxygenase pathway, through use of endogenous or exogenous substrate, leads to a very rapid, irreversible inactivation of this enzyme. The lipoxygenase pathway is also progressively impaired, but much less rapidly than the cyclooxygenase enzyme and much less markedly on use of exogenous compared to endogenous substrate. The possible consequences of these physiological processes of spontaneous inactivation are considered.

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“…Catalase and lysosomal enzymes were measured using standard assays (24,25). The conversion of arachidonic acid by washed platelets was assessed after stirring of the cells with the fatty acid for 5 min, using both quantitative gas chromatography mass spectrometry, and by assessing conversion of labeled [I4C]arachidonic acid, using thin layer chromatographic separation of products as described earlier (26).…”

Section: Methodsmentioning

confidence: 99%

Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules.

Gerrard¹,

Phillips²,

Rao³

et al. 1980

J. Clin. Invest.

277

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Cyclic AMP and platelet prostaglandin synthesis

Cited by 93 publications

References 8 publications

Synergistic activation by collagen and 15-hydroxy-9 alpha,11 alpha-peroxidoprosta-5,13-dienoic acid (PGH2) of phosphatidylinositol metabolism and arachidonic acid release in human platelets.

Synergistic activation by collagen and 15-hydroxy-9 alpha,11 alpha-peroxidoprosta-5,13-dienoic acid (PGH2) of phosphatidylinositol metabolism and arachidonic acid release in human platelets.

Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets

Biochemical studies of two patients with the gray platelet syndrome. Selective deficiency of platelet alpha granules.

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