The presence of diadenosine 5′,5‴-P 1 ,P 3 -triphosphate (Ap 3 A) in human platelets

Lüthje, Jürgen; Ogilvie, Adaling

doi:10.1016/0006-291x(83)90997-x

Cited by 156 publications

(65 citation statements)

References 12 publications

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“…43 Platelets interact with coagulation factors, in particular thrombin, a potent platelet-activating agonist, 44 and during thrombin-induced aggregation, almost the entire content of platelet granules is released. 45,46 Platelets from patients with renal failure have increased intracellular concentration of the diadenosine polyphosphates. Diadenosine pentaphosphate (Ap 5 A) and diadenosine hexaphosphate (Ap 6 A) act as strong growth factors for vascular smooth muscle cells (VSMC) via P2Y receptors.…”

Section: Other Effectsmentioning

confidence: 99%

A Bench to Bedside View of Uremic Toxins

Vanholder¹,

Baurmeister²,

Brunet³

et al. 2008

Journal of the American Society of Nephrology

315

231

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Section: Other Effectsmentioning

confidence: 99%

A Bench to Bedside View of Uremic Toxins

Vanholder¹,

Baurmeister²,

Brunet³

et al. 2008

Journal of the American Society of Nephrology

315

231

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“…The dinucleotides AP3A, AP4A, AP5A and AP6A are found in platelets and are released during aggregation (Flodgaard & Klenow, 1982;Luthje & Ogilvie, 1983;Schluter et al, 1994); the latter three are also found in adrenal medullary chromaffin granules, where they are stored in and released from secretory granules (Rodriguez del Castillo et al, 1988;Pintor et al, 1991;1992b); possibilities that remain to be investigated are whether or not they are contained in a releasable form in endocardial cells or in terminals of neurones innervating the heart.…”

Section: Degradation Of Nucleotides By Atrial Tissuementioning

confidence: 99%

“…Naturally occurring diadenosine polyphosphates have a chain length varying from three to six phosphate groups (Hoyle, 1990;Pintor et al, 1992b;Schluter et al, 1994), and the synthetic compound pyrophosphate (AP2A) completes an homologous series. They are found in platelets, and are released upon degranulation (Flodgaard & Klenow, 1982;Luthje & Ogilvie, 1983;Schluter et al, 1994), and they can act either on endothelial cells or vascular smooth muscle cells, thereby exerting a control over vascular tone. P',P3-di(adenosine) triphosphate (AP3A) mediates endothelium-dependent vasodilatation in the rat mesenteric artery , and endotheliumindependent vasodilatation in the rabbit mesenteric artery (Busse et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

The activation of P₁‐ and P₂‐purinoceptors in the guinea‐pig left atrium by diadenosine polyphosphates

Hoyle

Зиганшин

Pintor

et al. 1996

British J Pharmacology

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1 The effects of P', P2-di(adenosine) pyrophosphate (AP2A), P',P3-di(adenosine) triphosphate (AP3A), P',P"-di(adenosine) tetraphosphate (AP4A), P',P5-di(adenosine) pentaphosphate (AP5A), ATP, a,,Bmethylene ADP and 2-chloroadenosine (2-ClAd) were examined in the guinea-pig driven left atrium.2 All these purine compounds except a,#-methylene ADP produced a negative inotropic response with a rank order of potency of: 2-ClAd > > AP2A > ATP > AP4A = AP3A = AP5A. The ECs, value for 2-ClAd was approximately 1 guM, while those for the remaining compounds were in the range 10 guM-100 MM, a,f,-Methylene ADP (10-300 gM), a selective P2Y-purinoceptor agonist, produced a small positive inotropism.3 The P1-purinoceptor antagonist, 8-para-sulphophenyltheophylline 20 gM) caused a rightward shift in the concentration-response curves for 2-ClAd, ATP and AP2A, but converted the responses of AP3A, AP4A, and AP5A into positive inotropisms.4 The non-selective P2-purinoceptor antagonist, suramin (300 gM), had no significant effect on the concentration-response curves for 2-ClAd, ATP or AP2A, but significantly antagonized inhibitory responses to AP3A, AP4A and AP5A, and excitatory responses to a,,B-methylene ADP.5 In the presence of 8-pSPT (20 gM), suramin (300 gM) abolished the positive inotropic responses evoked by the dinucleotides. 6 ATP was degraded far more rapidly than any of the dinucleotides, and AP3A was the least stable of the diadenosine compounds. The relative order of stability was AP2A > AP4A = AP5A > AP3A > > ATP.Suramin (300 gM) reduced the rate of degradation of ATP and AP3A by approximately 30%. Suramin had no significant effect on the degradation of AP2A, AP4A or AP5A.7 It is concluded that the diadenosine polyphosphates cause negative inotropic responses via PIpurinoceptors and a hitherto undefined suramin-sensitive P2-purinoceptor, and that they appear to have positive inotropic effects mediated via another suramin-sensitive P2-purinoceptor.

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“…Apart from the presence of dinucleoside polyphosphates in crustaceans as previously indicated, these molecules were found as putative active vasoactive compounds when they were discovered in platelet secretory granules (Flodgaard and Klenow, 1982;Luthje and Ogilvie, 1983). From the moment they were discovered the main interest of the scientific community was to identify those actions triggered by the dinucleotides in the blood stream.…”

Section: Presence and Extracellular Actions Of Dinucleoside Polyphospmentioning

confidence: 96%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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The presence of diadenosine 5′,5‴-P 1 ,P 3 -triphosphate (Ap 3 A) in human platelets

Cited by 156 publications

References 12 publications

A Bench to Bedside View of Uremic Toxins

A Bench to Bedside View of Uremic Toxins

The activation of P₁‐ and P₂‐purinoceptors in the guinea‐pig left atrium by diadenosine polyphosphates

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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The presence of diadenosine 5′,5‴-P 1 ,P 3 -triphosphate (Ap 3 A) in human platelets

Cited by 156 publications

References 12 publications

A Bench to Bedside View of Uremic Toxins

A Bench to Bedside View of Uremic Toxins

The activation of P1‐ and P2‐purinoceptors in the guinea‐pig left atrium by diadenosine polyphosphates

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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Product

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The activation of P₁‐ and P₂‐purinoceptors in the guinea‐pig left atrium by diadenosine polyphosphates