Dipyridamole inhibition of adenosine metabolism in human blood

Klabunde, Richard E.

doi:10.1016/0014-2999(83)90026-2

Cited by 253 publications

(92 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The identification of an adenosine receptor in the carotid body (McQueen & Ribeiro, 1981, 1983 and the observation of the effects of adenosine which we have described raise the question of whether adenosine has any physiological role in the regulation of respiration particularly in response to hypoxia. Hypoxia leads to increased adenosine production in a number of organs (Fox et al, 1974;Winn et al, 1979;Dobson et al, 1971) but it is not known if this occurs in the carotid body.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Adenosine stimulates respiration in man.

Watt¹,

Routledge²

1985

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 87%

“…The observed effects are transient as the half-life of adenosine in human blood at 370 C is less than 10 s (Klabunde, 1983). To our knowledge, there has been no other study examining the respiratory stimulant effects of intravenous adenosine in man.…”

Section: Discussionmentioning

confidence: 90%

Adenosine stimulates respiration in man.

Watt¹,

Routledge²

1985

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Adenosine is a potent inhibitor of platelet aggregation and an effective vasodilator. In whole blood adenosine and inosine are rapidly taken up via the nucleoside transporter of the blood cells [19]. Inside the cells the nucleosides are rephosphorylated [20].…”

Section: Metabolic Fate Of the Dinucleotides In Whole Bloodmentioning

confidence: 99%

Catabolism of Ap₄A and Ap₃A in whole blood

Lüthje

Ogilvie

1988

European Journal of Biochemistry

View full text Add to dashboard Cite

Adenosine(5')tetraphospho(5')adenosine (Ap4A) and adenosine(5')triphospho(5')adenosine (Ap3A) are stored in large amounts in human platelets. After activation of the platelets both dinucleotides are released into the extracellular milieu where they play a role in the modulation of platelet aggregation and also in the regulation of the vasotone. It has recently been shown that the dinucleotides are degraded by enzymes present in the plasma [Luthje, J. & Ogilvie, A. (1987) Eur. J . Biochem. 169, 385-3881. The further metabolism as well as the role of blood cells has not been established. The dinucleotides were first degraded by plasma phosphodiesterases yielding ATP (ADP) plus AMP as products which were then metabolized to adenosine and inosine. The nucleosides did not accumulate but were very rapidly salvaged by erythrocytes yielding intracellular ATP as the main product.Although lysates of platelets, leucocytes and red blood cells contained large amounts of Ap3A-degrading and Ap4A-degrading activities, these activities were not detectable in suspensions of intact cells suggesting the lack of dinucleotide-hydrolyzing ectoenzymes. Compared to ATP, which is rapidly degraded by ectoenzymes present on blood cells, the half-life of Ap4A was two to three times longer.Since the dinucleotides are secreted together with ADP and ATP from the platelets, we tested the influence of ATP on the rate of degradation of Ap4A. ATP at concentrations present during platelet aggregation strongly inhibited the degradation of Ap,A in whole blood. It is suggested that in vivo the dinucleotides are protected from degradation immediately after their release. They may thus survive for rather long times and may act as signals even at sites far away from the platelet aggregate.Adenosine(5')tetraphospho(5')adenosine (Ap,A) and the homologue adenosine( 5')triphospho(5')adenosine (Ap3A) are stored in large amounts in human platelets [l, 21. Both dinucleotides are released from the platelet dense granules into the extracellular milieu after activation of the cells [l, 21. Ap3A and Ap4A have been suggested to play a role in platelet physiology. Ap4A inhibits ADP-induced platelet aggregation in platelet-rich plasma as well as in whole blood [3, 41. In contrast, Ap3A causes a gradual aggregation of platelets. This Ap3A-induced aggregation is mediated by an enzymatic activity in plasma that hydrolyzes Ap3A, producing ADP, a potent stimulator of platelet aggregation [4]. Furthermore, previous results have shown that Ap4A and Ap3A not only modulate platelet aggregation but also have vasomotor effects [5]. Thus, increasing experimental evidence suggests that these dinucleotides are regulatory molecules involved in the complex process of hemostasis.With respect to their possible role as extracellular signals it is of interest to know how long the dinucleotides can survive Enzymes. The enzymes in the plasma splitting Ap,A and Ap4A are 5'-nucleotide phosphodiesterases (EC 3.1.4.1); lactate dehydrogenase (EC 1.1.1.27).in the blood stream. After their releas...

show abstract

“…However, the concentrations of adenosine and NECA that caused half maximum heat production were about 100 times higher than those previously reported to activate platelet adenylate cyclase (Haslam & Rosson, 1975;Ukena et al, \ * 1985). The possibility that the response to adenosine occurred via a direct metabolic effect on the platelets and not via a receptor site was investigated using the adenosine uptake inhibitor dipyridamole (Klabunde, 1983). This agent did not modify the response to administered adeno-1.0 10 sine and had no effect by itself on platelet metaitration (mM) bolism.…”

Section: Discussionmentioning

confidence: 90%

Microcalorimetric studies on the effect of adenosine receptor agonists and xanthine derivatives on overall metabolism in human platelets.

Edvinsson¹,

Ikomi-Kumm²,

Monti³

1986

Brit J Clinical Pharma

View full text Add to dashboard Cite

Sweden1 The direct overall metabolic effects of drugs acting on adenosine receptors in human platelets were evaluated using a sensitive microcalorimetric method. 2 Adenosine induced a concentration-dependent increase in the heat production rate at concentrations above 100 FM. The adenosine uptake inhibitor, dipyridamole (3 FLM) did not modify the effect of adenosine. 3 Two putative adenosine receptor agonists were tested: NECA (5-N-ethyl carboxamide adenosine) and PIA (L-N6-phenylisopropyl-adenosine). NECA induced, at significantly lower concentrations than adenosine, an enhanced heat production rate. Concentrations above 1 mm had no effect. PIA, on the other hand, invariably induced a reduction in the heat production rate already at a concentration of 100 FLM.4 The two xanthine derivatives enprofylline (25 FM) and theophylline (100 tLM) were tested at concentrations found during antiasthmatic therapy. Neither had any thermogenic effect by themselves nor showed any significant modification of the heat production rate induced by adenosine (300 FLM). 5 These results indicate that adenosine and NECA increase human platelet metabolism, whereas PIA has an opposite effect. The proposed adenosine receptor antagonists enprofylline and theophylline were without effects. This microcalorimetric study gives new insights into the complex nature of adenosine mechanisms in a human test system and indicates that the thermogenic effect of adenosine is unrelated to adenosine receptors.Keywords human platelets microcalorimetry adenosine metabolism heat production rate

show abstract

Dipyridamole inhibition of adenosine metabolism in human blood

Cited by 253 publications

References 13 publications

Adenosine stimulates respiration in man.

Adenosine stimulates respiration in man.

Catabolism of Ap₄A and Ap₃A in whole blood

Microcalorimetric studies on the effect of adenosine receptor agonists and xanthine derivatives on overall metabolism in human platelets.

Contact Info

Product

Resources

About

Dipyridamole inhibition of adenosine metabolism in human blood

Cited by 253 publications

References 13 publications

Adenosine stimulates respiration in man.

Adenosine stimulates respiration in man.

Catabolism of Ap4A and Ap3A in whole blood

Microcalorimetric studies on the effect of adenosine receptor agonists and xanthine derivatives on overall metabolism in human platelets.

Contact Info

Product

Resources

About

Catabolism of Ap₄A and Ap₃A in whole blood