Selective inhibition of thromboxane A2 biosynthesis in blood platelets

Gryglewski, Ryszard J.; Zmuda, A; Korbut, R; Krȩcioch, Ewa; Bieroń, K

doi:10.1038/267627a0

Cited by 60 publications

(15 citation statements)

References 18 publications

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“…Several thromboxane synthetase inhibitors (imidazole, N-0164. PG endoperoxide analogs, OKY-1581, and other pyridine derivatives) have been used experimentally to elucidate the role of TxA 2 (Needleman et al, 1977a(Needleman et al, , 1977bGorman et al, 1977;Gryglewski et al, 1977;Nijkamp et al, 1977;Miyamoto et al, 1980). Perfusion of rabbit kidneys from animals that had undergone ureter obstruction (hydronephrosis) for several days results in the release of exaggerated levels of PGE 2 when stimulated with vasoactive peptides (Nishikawa et al, 1977).…”

Section: Akiyoshi Kawasaki and Philip Needlemanmentioning

confidence: 99%

Contribution of thromboxane to renal resistance changes in the isolated perfused hydronephrotic rabbit kidney.

Kawasaki¹,

Needleman²

1982

Circulation Research

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SUMMARY. Thromboxane A 2 is not produced in normal rabbit kidneys, but its synthesis is induced in numerous renal pathological states. The presence of this potent vasoconstrictor could readily compromise renal hemodynamics. We found that the thromboxane synthetase inhibitor, OKY-1581 (sodium-3-[4,3-pyridylmethyl)phenyI]-2-methylacrylate) is effective in the perfused hydronephrotic kidney in selectively inhibiting thromboxane production without altering prostaglandin E2 or prostacyclin release. The vasoactive peptides bradykinin and angiotensin cause the hydronephrotic kidney to produce thromboxane A2, which results in a profound renal vasoconstriction which is reversed by pretreatment with OKY-1581. Thus, OKY-1581 provides a powerful tool which can be used to assess the participation of thromboxane in pathophysiological states and to ascertain the therapeutic potential of thromboxane synthetase inhibitors in numerous disease states. (Circ Res 50: [486][487][488][489][490] 1982)

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Section: Akiyoshi Kawasaki and Philip Needlemanmentioning

confidence: 99%

Contribution of thromboxane to renal resistance changes in the isolated perfused hydronephrotic rabbit kidney.

Kawasaki¹,

Needleman²

1982

Circulation Research

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“…In the present study, the effects of indomethacin, an inhibitor of cyclo-oxygenase, and of L8027, an inhibitor of thromboxane synthetase (Gryglewski, Zmuda, Korbut, Krecioch & Bieron, 1977) have been investigated in two in vitro models of anaphylaxis: the antigen-induced contraction of airway smooth muscle (trachea) and the release of histamine and SRS-A from chopped lung fragments. Some of the results were presented at the Seventh International Congress of Pharmacology (Hitchcock, 1978b Male albino guinea-pigs (Hartley strain, 250 g) were actively sensitized with a single injection (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the Antigen‐induced Contraction of Guinea‐pig Trachea and Immunological Release of Histamine and Srs‐a From Sensitized Guinea‐pig Lung by (2‐isopropyl‐3‐indolyl)‐3 Pyridyl Ketone (L8027) and Indomethacin

Hitchcock

1980

British J Pharmacology

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I (2-Isopropyl-3-indolyl-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen-and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine.5 Prostaglandins E and F2.2 were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F22, at rest and during contraction.Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2, have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.

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“…Indeed, since the extract's contractile effect was shown to be antagonized by mepyramine, methysergide and imidazole (Table l), it is possible to suggest that this effect is mediated by histamine, 5-hydroxytryptamine and arachidonic acid derivatives. Moreover, since imidazole is known to inhibit thromboxane synthetase (Gryglewski et al, 1977), it is possible to suggest that it is mediated by thromboxane A2. The order of potency of such involvement being: histamine > thromboxane A2 > 5 hydroxytryptamine.…”

Section: Discussionmentioning

confidence: 99%

Effects of Olea europaea L. extract on the rat isolated ileum and trachea

Fehri¹,

S²,

Aiache³

et al. 1995

Phytotherapy Research

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The effects of an Olea europaea L. dried leaf extract containing 3.2% of oleuropein were investigated on the rat isolated ileum and trachea. On basal tone rat isolated ileum, Olea europaea L. extract was shown to produce a dual effect characterized by a contraction at low doses (10-7-10-4g/mL) and a relaxation at high doses (3.10-4-10-3g/mL). The extract induced contractile effect was found to involve at least histamine, 5-hydroxytryptamine and thromboxane A2. On precontracted rat isolated ileum, the extract only induced a relaxation that was not modified by nifedipine, diltiazem, dipyridamone, verapamil or papaverine ( M). The effects of the extract were also studied on the rat isolated trachea. On basal tone organs, Ofea europaea L. extract did not produce any effect, whereas, when basal tone was raised by acetylcholine (ACh M), the drug caused a relaxation (maximal effect 39.01%&5.40°/~ of the response to theophylline; (3.10X ~O -' M n=15). It is suggested that the induced relaxation is consecutive to an increase of intracellular 3'5' CAMP.

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Selective inhibition of thromboxane A2 biosynthesis in blood platelets

Cited by 60 publications

References 18 publications

Contribution of thromboxane to renal resistance changes in the isolated perfused hydronephrotic rabbit kidney.

Contribution of thromboxane to renal resistance changes in the isolated perfused hydronephrotic rabbit kidney.

Stimulation of the Antigen‐induced Contraction of Guinea‐pig Trachea and Immunological Release of Histamine and Srs‐a From Sensitized Guinea‐pig Lung by (2‐isopropyl‐3‐indolyl)‐3 Pyridyl Ketone (L8027) and Indomethacin

Effects of Olea europaea L. extract on the rat isolated ileum and trachea

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