Characterization of platelet thromboxane A2/prostaglandin H2 receptor by a novel thromboxane receptor antagonist, [3H]S-145

Hanasaki, Kohji; Nagasaki, T.; Arita, Hitoshi

doi:10.1016/0006-2952(89)90501-7

Cited by 40 publications

(20 citation statements)

References 20 publications

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“…Unfortunately, S-145 has been reported to have partial agonistic activity in rat and human platelets and cat cerebral arteries [6,10,12], and we also confirmed this with guinea pig lung parenchy mal strips when it was added to the organ bath at more than 10 nM, although the development of tension by S-1452 was transient and followed by a reduction in basal inher ent tone (data not shown). However, when administered orally but not intravenously to guinea pigs at doses ranging from 0.1 to 10 mg/kg, no agonistic activity was observed (data not shown), suggesting that S-1452 might not have any adverse clinical consequences as an oral drug.…”

Section: Discussionsupporting

confidence: 73%

“…2). In contrast, the suppression of U-46619-evoked aggregation of human platelets [10] and contractions of monkey and cat cerebral arteries [12] and guinea pig trachea [31] by S-145 has been shown to be in a noncompetitive manner, which is presumably due to the extremely slow dissociation rate of S-145 from its re ceptor [10,11]. Why the antagonistic manner of this com pound differs between guinea pig lung parenchyma and other preparations is not yet clear.…”

Section: Discussionmentioning

confidence: 95%

“…However, when administered orally but not intravenously to guinea pigs at doses ranging from 0.1 to 10 mg/kg, no agonistic activity was observed (data not shown), suggesting that S-1452 might not have any adverse clinical consequences as an oral drug. An ex planation for the abolishment of the agonistic acitivity of S-1452 by oral administration comes from an in vitro study finding [10] in which the partial agonistic action in plate lets could be canceled by the repeated pretreatment of platelets with low concentrations of S-145 or by a gradual increase in S-145 concentrations, indicating that the grad ual occupation of TxA2 receptor by S-145 causes desensiti zation. In guinea pig lung parenchymal strips, the partial agonist of S-1452 was also abolished by a gradual increase in S-1452 concentrations (data not shown), although the contractile response to a TxA2 mimetic, U-46619, was in creased by successive increases in U-46619 concentrations ( % 2).…”

Section: Discussionmentioning

confidence: 99%

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Antiasthmatic Activity of a Novel Thromboxane A<sub>2</sub> Antagonist, S-1452, in Guinea Pigs

Arimura¹,

Asanuma²,

Kurosawa³

et al. 1992

Int Arch Allergy Immunol

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We examined the effect of a potent thromboxane (Tx) A₂ receptor antagonist, calcium (1R, 2S, 3S, 4S)-(5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)-5-heptenoate dihydrate (S-1452), on antigen- and various allergic-spasmogen-induced contractions of guinea pig lung parenchymal strips and on the increase in insufflation pressure, an index of bronchoconstriction, in anesthetized guinea pigs. In isolated guinea pig lung parenchymal strips, S-1452 showed competitive antagonism of the contractile activity of U-46619, a TxA2 mimetic, with a pA₂ value of 8.9. The compound also inhibited the contraction induced by prostaglandin (PG) D₂ and PGF_2α, but a TxA₂ synthetase inhibitor, OKY-046, did not. In contrast, both drugs inhibited not only leukotriene (LT) D₄-induced contraction but also antigen-induced contraction in the presence of a histamine antagonist. In anesthetized guinea pigs, oral administration of S-1452 markedly inhibited the bronchoconstrictions induced by intravenous injection of U-46619, PGD₂, PGF_2α, LTD₄ and platelet-activating factor (PAF) with ED₅₀ values of 0.006, 0.031, 0.112, 0.033 and 0.115 mg/kg, respectively, but OKY-046 inhibited only that by LTD₄ and PAF. Additionally, bronchoconstriction following intravenous injection of antigen was almost completely suppressed by S-1452 (0.1 mg/kg) and partially by OKY-046 (300 mg/kg) in passively sensitized guinea pigs which were treated with diphenhydramine and propranolol. The inhibitory effect of S-1452 against U-46619-induced bronchoconstriction persisted up to 7 h after oral administration. These results indicate that the dramatic improvement in bronchoconstriction in response to antigen by S-1452 results from the potent and long-lasting inhibition of contractile responses by various allergic mediators which act directly or indirectly via stimulation of TxA₂ receptors.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Antiasthmatic Activity of a Novel Thromboxane A<sub>2</sub> Antagonist, S-1452, in Guinea Pigs

Arimura¹,

Asanuma²,

Kurosawa³

et al. 1992

Int Arch Allergy Immunol

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“…The selective TX A 2 (TXA 2 ) synthase inhibitor OKY-046 ((E)-3[p-(1H-imidazol-ylmethyl)-phenil]-2-propenoic acid) was obtained from Kissei Pharmaceutical Co. Ltd. (Osaka, Japan). The TXA 2 receptor antagonist S-1452 [11](calcium (1R, 2S, 3S, 4S)-(5Z)-7(((phenylsulfonyl) amino)-bicyclo-(2.2.1)-hept-2-yl) hept-5-heptenoate dihydrate), was supplied from Shionogi Pharmaceutical Co. Ltd. (Osaka, Japan). FR167653 [12], a dual inhibitor of TNF-α and IL-1β synthesis, was provided by Fujisawa Pharmaceutical Co. Ltd. (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Effects of Selective Cyclooxygenase Inhibitors on Ischemia/Reperfusion-Induced Hepatic Microcirculatory Dysfunction in Mice

Yoshiya

Katagiri²,

Ishii³

et al. 2003

Eur Surg Res

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We examined the effects of selective cyclooxygenase (COX) inhibition on hepatic warm ischemia/reperfusion (I/R) injury in mice. A selective COX-1 inhibitor, SC-560, selective COX-2 inhibitors, NS-398 and celecoxib, and indomethacin were administered 30 min before ischemia. Four hours after reperfusion, an in vivo microscopic study showed that I/R caused significant accumulation of leukocytes adhering to the hepatic microvessels and nonperfused sinusoids. Levels of plasma alanine transaminase (ALT) and tumor necrosis factor (TNF)-α also showed increases. SC-560, NS-398, celecoxib and indomethacin significantly reduced hepatic responses to I/R including microcirculatory dysfunction and release of ALT and TNF-α. Moreover, the effects of the thromboxane (TX) A₂ (TXA₂) synthase inhibitor OKY-046 and the TXA₂ receptor antagonist S-1452 on hepatic responses to I/R exhibited results similar to those obtained with COX inhibitors. These results suggest that COX-1 and COX-2 contribute to I/R-induced hepatic microvascular and hepatocellular injury partly through TNF-α production, and that TXs derived from COX are partly responsible for I/R-induced liver injury.

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“…S-145 has been found to be an effective blocker of TXA2-induced platelet aggregation and vasoconstriction and to protect against collagen-induced ECG changes and thrombopenia and experimental bronchial asthma in rodents. [25][26][27][28][29][30] Permanent middle cerebral artery (MCA) occlusion models in the rat have generally been used to assess the protective effects of various drugs against ischemic brain damage.31'32 However, in human ischemic stroke, there is a possibility that recirculation occurs frequently after focal ischemia, particularly in the case of cerebral embolism. Thus, a recirculation model after MCA occlusion may be useful for simulating focal ischemia in humans.…”

mentioning

confidence: 99%

Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats.

Matsuo

Izumiyama

Oda

et al. 1993

Stroke

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Background and Purpose: Arachidonate metabolites have been implicated in the development of cerebral injury after ischemia. Particular importance has been placed on the balance of thromboxane A2 and prostaglandin 12 because of its regulative activity on platelet functions and arterial tone. The purpose of the present study was to shed light on the role of thromboxane A2 in postischemic brain injury.Methods: We evaluated the effects of S-1452, a novel thromboxane A2 receptor antagonist, on brain edema, infarct areas, and survival rate in rats with middle cerebral artery occlusion. A transient middle cerebral artery occlusion model was produced by inserting a piece of silicon-coated nylon thread into the internal carotid artery.Results: The ratio of plasma thromboxane B2 to 6-keto-prostaglandin Fi, significantly rose at 0 hour (P<.05), 1 hour (P<.01), 3 hours (P<.05), and 12 hours (P<.05) and then nearly returned to the normal level at 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (5, 10, or 50 mg/kg PO) significantly attenuated the increase in postischemic water content in the cerebral cortex perfused by the anterior cerebral artery and the cerebral cortex perfused by the middle cerebral artery in a dose-dependent manner but slightly attenuated it in the caudate putamen 24 hours after reperfusion following 1-hour occlusion. Pretreatment with S-1452 (10 mg/kg PO) also significantly decreased the areas of infarction in the front parts of the cerebrum. The survival rate of animals after 2 hours of occlusion tended to be improved by treatment with S-1452 (10 mg * kg`d`PO), although there was no statistical significance.Conclusions: Our results suggest that thromboxane A2 is closely related to postischemic brain injury in the early phase of recirculation and that S-1452 may have a protective effect on postischemic brain injury. (Stroke. 1993;24:2059-2065 Approximately 30% of the experimental animals were excluded by the above reasons, and the rest (approximately 70%) of the experimental animals were used as ischemic animals in further study.After 1 or 2 hours of MCA occlusion, the thread was removed to allow complete reperfusion of the ischemic area via the right common carotid artery (CCA).Rats were decapitated at 0 hour (just after reperfusion), 1 hour, 3 hours, 6 hours, 12 hours, and 24 hours after reperfusion following 1-hour transient MCA occlusion. For measurement of brain water content, brain samples of both hemispheres were taken from the cerebral cortex perfused by the anterior cerebral artery (ACA area), the cerebral cortex perfused by the MCA (MCA area), and the caudate putamen. The water content of these samples was calculated as follows: 100x (wet weight-dry weight)/wet weight (%). MCA and ACA areas were defined as described by Nagasawa and Kogure.34 Before the experiment, the extent of the

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Characterization of platelet thromboxane A2/prostaglandin H2 receptor by a novel thromboxane receptor antagonist, [3H]S-145

Cited by 40 publications

References 20 publications

Antiasthmatic Activity of a Novel Thromboxane A<sub>2</sub> Antagonist, S-1452, in Guinea Pigs

Antiasthmatic Activity of a Novel Thromboxane A<sub>2</sub> Antagonist, S-1452, in Guinea Pigs

Effects of Selective Cyclooxygenase Inhibitors on Ischemia/Reperfusion-Induced Hepatic Microcirculatory Dysfunction in Mice

Effect of a novel thromboxane A2 receptor antagonist, S-1452, on postischemic brain injury in rats.

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