Effect of prostaglandin E1 on platelet behaviour in vitro and in vivo.

Emmons, Patricia; Hampton, John R.; Harrison, M. J. G.; Honour, A. J.; Mitchell, J. R. A.

doi:10.1136/bmj.2.5550.468

Cited by 176 publications

(36 citation statements)

References 11 publications

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“…In later experiments uptake was determined after incubation for 1 h. As adrenaline can cause aggregation of platelets in plasma, prostaglandin E1 (2-8 x 10-7M) which had no effect on adrenaline uptake (Table 1) the platelet-rich plasma to inhibit aggregation (Emmons, Hampton, Harrison, Honour & Mitchell, 1967). The uptake of intact [3H]-adrenaline was proportional to the concentration of extracellular adrenaline up to about 1 x 10-4M; with higher concentrations the proportionality decreased (Fig.…”

Section: Resultsmentioning

confidence: 99%

Uptake, metabolism and release of [³H]‐adrenaline by human platelets

Born

Smith

1970

British J Pharmacology

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Summary1. Measurements were made of the uptake, metabolism and release of [3H]-adrenaline by human platelets in citrated plasma or in an artificial medium. 2. Radioactive adrenaline was not taken up at 0-2°C. At 370 C there was a slow uptake which continued for at least 5 hours.3. About half of the radioactivity in the platelets was intact adrenaline. The other half was an acidic metabolite from which adrenaline was released by acid hydrolysis. 4. The immediate uptake of adrenaline was proportional to its concentration in the plasma up to at least 1 x 1O-5M. Uptake measured after 1 h also increased linearly with concentration up to about 1 x 10-4M but less with higher concentrations. The highest concentration ratio was about 12. 5. The concentration of metabolite in the platelets increased with the concentration of added adrenaline only up to about 2 x 10-m. 6. The immediate uptake of adrenaline was partially inhibited by phentolamine and dihydroergotamine. Measurement of uptake both immediately and after 1 h showed that the inhibition produced was not increased beyond about 50% by these drugs or by (±)-propranolol, chlorpromazine or amitriptyline up to 1 x 10 'M. 7. Formation of the metabolite was inhibited by pyrogallol, 8-hydroxyquinoline, or tropolone. This inhibition was associated with a corresponding increase in the adrenaline accumulated intact. Formation of the metabolite was not inhibited by monoamine oxidase inhibitors. 8. Reserpine caused a small decrease in the uptake of adrenaline radioactivity in 1 h and a great increase in the proportion recovered as metabolite. 9. Thrombin caused the release from platelets of intact adrenaline but not of the metabolite. 10. Platelets of albino patients with spontaneous haemorrhages accumulated adrenaline radioactivity at the normal rate but this radioactivity was wholly accounted for by metabolite and not released by thrombin. 11. After taking up adrenaline, platelets resuspended in artificial medium at 370 C slowly released both adrenaline and its metabolite. At the same time, the intracellular adrenaline was slowly metabolized.

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Section: Resultsmentioning

confidence: 99%

Uptake, metabolism and release of [³H]‐adrenaline by human platelets

Born

Smith

1970

British J Pharmacology

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“…Emmons, Hampton, Harrison, Honour & Mitchell (1967), first demonstrated that PGE1 inhibits platelet thrombus formation in vivo in injured rabbit-brain arteries. Westwick (1977) has now shown that both PGE1 and PGG2 inhibit thrombus formation in hamster cheek pouch arterioles.…”

Section: Introductionmentioning

confidence: 99%

PROSTACYCLIN (PGI₂) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH

Higgs

Moncada

et al. 1978

British J Pharmacology

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1 Isolated rings of hamster aorta produced an unstable substance which inhibited platelet aggregation in vitro and had the same characteristics as prostacyclin. 2 Prostacyclin inhibited adenosine diphosphate (ADP)-induced aggregation of hamster platelets in vitro.3 The effects of prostacyclin on ADP-induced platelet thrombi in the microcirculation of the hamster cheek pouch were studied with a television microscope. 4 Prostacyclin caused a dose-dependent increase in the time of iontophoretic application of ADP which was required to induce platelet thrombi formation and embolization in venules (30 to 40 gm diameter).5 Prostacyclin caused a dose-dependent reduction in the total time during which ADP-induced thrombi were observed following local electrical damage to arterioles (40 to 80 gm diameter). 6 Thrombus formation in venules and arterioles was abolished by 500 ng/ml prostacyclin in the Krebs solution superfusing the hamster cheek pouch. 7 Prostacyclin was approximately twenty times more potent than prostaglandin E1 in preventing thrombus formation in the microcirculation.

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“…Compounds which affect the activity of these enzymes and, as a result, the concentrations of adenosine 3',5'-monophosphate (cyclic AMP, cAMP) in platelets also have marked effects on platelet aggregation (2, 6-10) and on the platelet release reaction (11). For example, incubation of platelets with prostaglandin (PGE1), N6-2'-0-dibutyryl cyclic adenosine 3',5'-monophosphate (DBcAMP), or theophylline before addition of thrombin inhibits thrombin-induced platelet aggregation (9,10,12) and release (11). These observations have led to the hypothesis that agents which inhibit platelet aggregation increase the concentration of cAMP in platelets by stimulating adenyl cyclase or by inhibiting cAMP phosphodiesterase, and agents which stimulate aggregation and release, decrease platelet cAMP by the opposite mechanisms.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

Brodie¹,

Baenziger²,

Chase³

et al. 1972

J. Clin. Invest.

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A B S T R A C T Washed human platelets were incubated with 0.1-1.0 U/ml human thrombin and the effects on adenyl cyclase activity and on a platelet membrane protein (designated thrombin-sensitive protein) were studied. Adenyl cyclase activity was decreased 70-90% when intact platelets were incubated with thrombin. The Ti for loss of adenyl cyclase activity was less than 15 sec at 1 U/ml thrombin. There was no decrease of adenyl cyclase activity when sonicated platelets or isolated membranes were incubated with these concentrations of thrombin. Loss of adenyl cyclase activity was relatively specific since the activities of other platelet membrane enzymes were unaffected by thrombin. Prior incubation of platelets with dibutyryl cyclic adenosine monophosphate (AMP), prostaglandin El, or theophylline protected adenyl cyclase from inhibition by thrombin.Incubation of intact but not disrupted platelets with thrombin resulted in the release of thrombin-sensitive protein from the platelet membrane. The rapid release of this protein (Ti < 15 sec) at low concentrations of thrombin suggested that removal of thrombin-sensitive protein from the platelet membrane is an integral part of the platelet release reaction. This hypothesis is supported by the parallel effects of thrombin on adenyl cyclase activity and thrombin-sensitive protein release in the presence of dibutyryl cyclic AMP, prostaglandin Ei, and theophylline at varying concentrations of thrombin.

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Effect of prostaglandin E1 on platelet behaviour in vitro and in vivo.

Cited by 176 publications

References 11 publications

Uptake, metabolism and release of [³H]‐adrenaline by human platelets

Uptake, metabolism and release of [³H]‐adrenaline by human platelets

PROSTACYCLIN (PGI₂) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH

The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

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Effect of prostaglandin E1 on platelet behaviour in vitro and in vivo.

Cited by 176 publications

References 11 publications

Uptake, metabolism and release of [3H]‐adrenaline by human platelets

Uptake, metabolism and release of [3H]‐adrenaline by human platelets

PROSTACYCLIN (PGI2) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH

The Effects of Thrombin on Adenyl Cyclase Activity and a Membrane Protein from Human Platelets

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Uptake, metabolism and release of [³H]‐adrenaline by human platelets

Uptake, metabolism and release of [³H]‐adrenaline by human platelets

PROSTACYCLIN (PGI₂) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH