Specific binding sites for prostaglandin D2 on human platelets

Siegl, Adelaide M.; Smith, J B; Silver, Melvin J.

doi:10.1016/0006-291x(79)91623-1

Cited by 51 publications

(12 citation statements)

References 11 publications

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“…Armstrong et al (1983) Armstrong et al (1983) on human platelets with [3H]-15(s)-9,1 l-epoxymethano-PGH2 (their value was 1,700 sites per platelet). This density was several times more than that found for the PGD2 receptor on human platelets (Siegl et al, 1979;Cooper & Ahern, 1979 Mais et al (1985a) found that U-46619 was a more potent aggregating agent than STA2 of human platelets (we also found that U-46619 was as potent as STA2), the observed order of displacing potency does not seem to fit with the biological activity. The reason for this discrepancy was not investigated in the present study but could be explained in several ways.…”

Section: Lacontrasting

confidence: 71%

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Narumiya¹,

Okuma

Ushikubi

1986

British J Pharmacology

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Binding of a 125I‐labelled derivative of the 13‐azapinane thromboxane antagonist (ONO‐11120), [125I]‐9,11‐dimethylmethano‐11,12‐methano‐16‐(3‐iodo‐4‐hydroxyphenyl)‐13,14‐dihydro‐13‐aza‐15‐β‐ω‐tetranor‐thromboxane A2 ([125I]‐PTA‐OH), to washed platelets of human, dog and rabbit was studied. Results were compared with the in vitro inhibitory potency of ONO‐11120 on platelet aggregation induced by arachidonate and a thromboxane agonist, 9,11‐epithio‐11,12‐methanothromboxane A2 (STA2). [125I]‐PTA‐OH bound to washed human platelets in a reversible, saturable and temperature‐dependent manner, and specific binding displaced by 20 μM ONO‐11120 constituted about 40% of the total binding. Scatchard analyses revealed a single class of specific binding and the equilibrium dissociation constant (KD) and maximal concentration of binding sites (Bmax) were 22 nM and 390 fmol per 108 platelets (about 2,300 sites per platelet), respectively. In addition to ONO‐11120, STA2 and another thromboxane receptor agonist, (15S)‐hydroxy‐11,9‐epoxymethano‐prosta‐5Z,13E‐dienoic acid (U‐46619), effectively displaced the binding with IC50 values of 44 and 125 nM respectively. Prostaglandin D2 (PGD2) partially displaced the binding only at a concentration above 1 μM. PGE1 and thromboxane B2 (TXB2) were without effect up to 100 μM. Similar binding of [125I]‐PTA‐OH was observed on dog platelets. The KD and Bmax were 12 nM and 110 fmol per 108 platelets (about 680 sites per platelet), respectively, and these values did not change significantly after adrenaline treatment which potentiated arachidonate‐induced aggregation of platelets in this species. On the other hand, no specific binding of [125I]‐PTA‐OH was found on rabbit platelets. Consistent with the results from binding studies, ONO‐11120, 0.5 μM, completely suppressed arachidonate‐induced aggregation of human platelets, whereas, at concentrations up to 5 μM, this agent did not significantly inhibit aggregation of rabbit platelets induced by the same stimulus. STA2‐induced aggregation of rabbit platelets also showed less sensitivity to ONO‐11120. When a similar extent of irreversible aggregation was induced by STA2 and the inhibitory potency of ONO‐11120 was compared in human and rabbit platelets, about one hundred times greater concentration of ONO‐11120 was required to suppress aggregation of rabbit platelets than that of human platelets. These results suggest that [125I]‐PTA‐OH binds to a platelet thromboxane receptor, and that the structure of the binding site(s) on the receptor may vary between species.

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Section: Lacontrasting

confidence: 71%

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Narumiya¹,

Okuma

Ushikubi

1986

British J Pharmacology

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“…A specific PGD2 receptor has been identified by radioligand receptor assay on one of them, i.e. human platelets (Schafer et al, 1979;Siegl et al, 1979) and BW245C has been shown to act on that receptor (Town et al, 1983). It, therefore, seems likely that responses of the other two tissues are mediated by the same type of PGD2 receptor.…”

Section: Discussionmentioning

confidence: 99%

“…It is also likely that PGD2 acts on other prostaglandin or thromboxane receptors to elicit responses in some of the systems. A specific PGD2 receptor was identified on human platelets by two groups using the radioligand receptor assay (Schafer et al, 1979;Siegl et al, 1979), and PGD2 blocks aggregation of platelets possibly by stimulating adenylate (Mills & Macfarlane, 1974;Feinstein et al, 1983). In other tissues, the presence of PGD2-specific receptor(s) has been suggested by the studies comparing its potency with those of other naturally occurring prostaglandins; these include arterial vascular bed of sheep (Jones, 1978), mast cells (Holgate et al, 1980) and rabbit stomach (Whittle et al, 1979).…”

Section: Introductionmentioning

confidence: 99%

Different responsiveness of prostaglandin D₂‐sensitive systems to prostaglandin D₂ and its analogues

Narumiya

Toda

1985

British J Pharmacology

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1 Prostaglandin D2 (PGD2) and six PGD2 analogues were used to classify responsiveness of several PGD2-sensitive systems. The analogues used were 9P-PGD2, 5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin (BW245C), 19,, PGD2 amide, PGD2 N-monomethylamide and 1 l-keto-I5o-hydroxy-A59"12-prostenoic acid (9-deoxy-A9"12-PGD2). The PGD2-sensitive systems examined were human platelets, rat peritoneal mast cells, rabbit transverse stomach strip, guinea-pig tracheal ring chain and helical strip of the dog cerebral artery.2 PGD2, 9p-PGD2 and BW245C inhibited the aggregation of human platelets, increased adenosine 3':5'-cyclic monophosphate (cyclic AMP) in rat mast cells and relaxed the rabbit stomach strip. The rank order of potency was BW245C> PGD2>9p-PGD2. PGD2 amide and PGD2 N-monomethylamide were inactive in the former two systems but elicited relaxant activity on the rabbit stomach strip. 17-Phenyl-PGD2 was virtually inactive in the above three systems. 3 PGD2 and 1 7-phenyl-PGD2 contracted the guinea-pig tracheal ring chain and the helical strip of dog cerebral arteries with almost equal potency. 9l-PGD2 and BW245C antagonized competitively the contractile action of PGD2. PGD2 amide and PGD2 N-monomethylamide showed weak agonistic actions in the tracheal preparation. 4 9-Deoxy-A9 I2-PGD2, showing stronger growth inhibition than PGD2 on cultured tumour cells, was inactive in human platelets, rat mast cells and guinea-pig trachea, and elicited contractile response in the rabbit stomach strip. 5 These results indicate the presence of three groups of PGD2-sensitive systems that respond differently to PGD2 and its analogues. IntroductionProstaglandin D2 (PGD2) is one of the prostaglandin which is ubiquitously formed and present in mammalian tissues (Nugteren & Hazelhof, 1973;Ikai et al., 1984). Various actions ofthis prostaglandin have been reported, which include the anti-aggregatory activity on platelets of several species (Whittle et al., 1978), the contraction of airway smooth muscle (Hamberg et al., 1975;Schneider & Drazen, 1980), inflammatory effects (Flower et al., 1976;Soter et al., 1983), and the action on mast cells (Holgate et al., 1980). PGD2 also induces either contractions or relaxations in several vascular and gastrointestinal smooth muscle preparations (Horton & Jones, 1974;Whittle et al., 1979;Toda, 1982a). Recently CNS effects ofthis prostaglan-'Author for correspondence. din such as hypothermia and induction of sleep have been reported in rodents (Ueno et al., 1982a, b). In addition, inhibition of tumour cell proliferation by PGD2 and its dehydration derivatives, 9-deoxy-A9-PGD2 and 9-deoxy-A9"2-PGD2 has also been described (Fukushima et al., 1982a,b;Kikawa et al., 1984). However, whether these actions are mediated via a single and identical PGD2 receptor or several PGD2 receptors exist for each action has remained unclarified. It is also likely that PGD2 acts on other prostaglandin or thromboxane receptors to elicit responses in some of the systems. A specific PGD2 receptor was identifi...

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“…A single class of binding sites in the platelet has been reported (84, [168][169][170]. A single class of binding sites in the platelet has been reported (84, [168][169][170].…”

Section: Radioligand Binding Studiesmentioning

confidence: 97%

Thromboxane, Prostaglandin and Leukotriene Receptors

Halushka

Mais²,

Mayeux³

et al. 1989

Annu. Rev. Pharmacol. Toxicol.

243

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Specific binding sites for prostaglandin D2 on human platelets

Cited by 51 publications

References 11 publications

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Different responsiveness of prostaglandin D₂‐sensitive systems to prostaglandin D₂ and its analogues

Thromboxane, Prostaglandin and Leukotriene Receptors

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Specific binding sites for prostaglandin D2 on human platelets

Cited by 51 publications

References 11 publications

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Binding of a radioiodinated 13‐azapinane thromboxane antagonist to platelets: correlation with antiaggregatory activity in different species

Different responsiveness of prostaglandin D2‐sensitive systems to prostaglandin D2 and its analogues

Thromboxane, Prostaglandin and Leukotriene Receptors

Contact Info

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Different responsiveness of prostaglandin D₂‐sensitive systems to prostaglandin D₂ and its analogues