Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:021133 (ATP)
 132,114 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Responses of the carotid artery of rabbits to intraluminal and abluminal administration of purinergic agonists were examined. The carotid artery was perfused in vitro and changes in diameter were recorded. 2. Intraluminal acetylcholine, ADP, and ATP produced pronounced vasodilatation, whereas abluminal acetylcholine, but not ADP and ATP, produced dilatation of phenylephrine-preconstricted arteries. Intra- and abluminal adenosine and nitroprusside produced equipotent vasodilatation. 3. N omega-nitro-L-arginine abolished dilator responses to acetylcholine and adenine nucleotides, and unmasked vasoconstrictor responses to high concentrations of these agonists. Responses to adenosine and nitroprusside were not affected by nitro-L-arginine. 4. Intraluminal, but not abluminal, administration of nucleotidase-resistant adenine nucleotide analogues 2-methylthio-ATP and ADP beta S produced significant vasodilation in arteries preconstricted with phenylephrine. Intra- and abluminal administration of alpha,beta-methylene-ATP, a potent P2X-purinoceptor agonist, did not produce vasodilatation in preconstricted arteries. 5. Abluminal ADP failed to elicit dilatation of phenylephrine-preconstricted arteries even in the presence of the ADPase inhibitor beta,gamma-methylene-ATP (10(-5)M). When P2X-purinoceptors, which mediate adenine nucleotide-induced vasoconstriction, were stimulated with alpha,beta-methylene-ATP (10(-5)M), abluminal ADP produced vasodilatation, presumably because P2X-purinoceptors were occupied, thereby unmasking P2Y-purinoceptor-mediated dilatation. 6. These results suggest that asymmetric vascular responses of rabbit carotid arteries to adenine nucleotides may be due in part to preferential activation of P2Y-purinergic receptors on endothelium and P2X-purinergic receptors on vascular smooth muscle.
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PMID:Asymmetry of vascular responses of perfused rabbit carotid artery to intraluminal and abluminal vasoactive stimuli. 130 65

In addition to its diverse functions inside cells, ATP can act at several types of cell-surface receptor. One of these (P2X-purinoceptor) is believed to be a ligand-gated cation channel. The presence of P2X receptors on autonomic, sensory and central neurons suggests that ATP might be released to act as a fast excitatory synaptic transmitter. Here we record excitatory synaptic potentials and currents from cultured coeliac ganglion neurons which are mimicked by ATP, blocked by the P2-purinoceptor antagonist suramin, desensitized by alpha,beta-methylene-ATP and unaffected by antagonists acting at nicotine, 5-hydroxytryptamine, N-methyl-D-aspartate (NMDA), non-NMDA glutamate, gamma-aminobutyric acid (GABA), noradrenaline or adenosine receptors. We conclude that ATP is the neurotransmitter at this neuroneuronal synapse.
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PMID:ATP mediates fast synaptic transmission in mammalian neurons. 135 59

1. The nature of the transmitter mediating vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation was studied. 2. Prazosin (0.1 microM) abolished the response to exogenously applied phenylephrine (1 microM) but had no effect on constrictions of submucosal arterioles evoked by nerve stimulation (100 pulses at 10 Hz). 3. Vasoconstrictions and excitatory junction potentials elicited by nerve stimulation were potentiated by idazoxan (0.1 microM). 4. Following reserpine treatment, catecholamine fluorescence was absent in submucosal arterioles but nerve-evoked vasoconstrictions were unaltered. 5. Vasoconstrictions and excitatory junction potentials recorded in response to sympathetic nerve stimulation, as well as constrictions evoked by exogenously applied ATP (3 microM), were abolished by the P2-purinoceptor antagonist, suramin (100 microM). Suramin had no effect on the vasoconstriction in response to noradrenaline (3 microM), or the nicotinic excitatory postsynaptic potentials (e.p.s.ps) and noradrenergic inhibitory postsynaptic potentials (i.p.s.ps) recorded from submucosal neurones. 6. We conclude that postjunctional responses of submucosal arterioles following sympathetic nerve stimulation are mediated solely through the activation of P2X-purinoceptors by ATP or a related purine nucleotide. The function of neurally released noradrenaline is to act through prejunctional alpha 2-adrenoceptors to depress transmitter release.
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PMID:Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP. 135 56

Membranes of the rat vas deferens were shown to contain a high density of binding sites for [3H] alpha, beta-methylene ATP ([3H] alpha, beta-MeATP), a ligand selective for the P2X purinoceptor. Analysis demonstrated two classes, of high affinity (Kd = 1.8 nM, Bmax (maximum density) = 9.3 pmol/mg of protein) and of low affinity (Kd = 34 nM, Bmax = 29 pmol/mg of protein). The high affinity [3H] alpha, beta-MeATP binding sites were successfully solubilized with 2% digitonin: the Kd was then 1.6 nM. Both the association and dissociation of the receptor-ligand complex were rapid (half-time for association = 6.5 min). The rank order of potency of purinergic ligands in displacing [3H] alpha, beta-MeATP binding from the solubilized preparation was in accord with the pharmacological criteria for P2X purinoceptors. The receptor-detergent complex was separated by sucrose gradient ultracentrifugation from the ATPase enzymes also present in the preparation. The sedimentation coefficient of the receptor-detergent complex was 12.1 S. It was shown that [3H] alpha, beta-MeATP can function as a photoaffinity labeling reagent upon exposure to ultraviolet light; in the rat vas deferens membranes, it thus became cross-linked in a specific manner to a polypeptide of apparent molecular mass = 62,000 daltons, proposed to be the ligand-binding subunit of the functional P2X purinoceptor.
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PMID:Solubilization and molecular size determination of the P2x purinoceptor from rat vas deferens. 138 37

Because various fetal anomalies are seen in diabetic offspring, we examined the effects of sugars on proteoglycans (PGs): extracellular matrix (ECM) macromolecules modulating morphogenesis. 13-d-old mouse metanephric kidney explants were exposed to mannose for 7 d and labeled with [35S]sulfate, [35S]-methionine, or [3H]thymidine. Mannose exposure caused reduction in kidney size and disorganization of ureteric bud branches with inhibition of glomerulogenesis. Tissue autoradiographic and immunofluorescence studies indicated decreased expression of sulfated PGs in ECMs. Helix pomatia lectin binding to D-GalNAc residues of glomerular epithelial cells was also reduced. Biochemical studies revealed decreased synthesis of sulfated PGs. PGs were of lower molecular weight with reduced charge density and increased chondroitin/heparan sulfate ratio. Immunoprecipitation of [35S]methionine-labeled proteins confirmed the reduction of PG core peptides. Intracellular ATP levels were reduced. The addition of 0.1 mM ATP to culture media restored kidney size, the population of glomeruli, and the synthesis and characteristics of PGs to almost normal, with no detectable effect on the replication of cells as determined by [3H]thymidine incorporation. The effect of ATP could be partially blocked by the P2y-purinoreceptor, i.e., reactive blue-2. Data suggest that mannose causes energy depletion by cellular ATP consumption and thus selectively alters the synthesis of heavily glycosylated proteins with rapid turnover, such as PGs, resulting in renal dysmorphogenesis.
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PMID:Mannose-induced dysmorphogenesis of metanephric kidney. Role of proteoglycans and adenosine triphosphate. 140 Oct 58

1. The activity of adenosine 5'-diphosphoribose (ADP-ribose), a ribosylated purine nucleotide, was investigated on the carbachol-contracted taenia coli, a tissue possessing P1- (A2) and P2Y-purinoceptors and on the guinea-pig vas deferens which possesses P2X-purinoceptors. 2. In the vas deferens, where ATP (1 microM-1 mM) produced concentration-dependent contractions, ADP-ribose was without effect at concentrations up to 1 mM. 3. In the taenia coli, ADP-ribose (0.1 microM-1 mM) produced concentration-dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD2 values for ADP-ribose, adenosine and ATP were 4.5 +/- 0.07 (27), 4.4 +/- 0.10 (9) and 5.5 +/- 0.14 (21), respectively. The time-course of the relaxations elicited by ADP-ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine. 4. The P1-purinoceptor antagonist, 8-phenyltheophylline (5 microM), produced parallel rightward shifts in the concentration-response curves of the relaxations of the taenia coli elicited by ADP-ribose and adenosine but not ATP. 5. Dipyridamole (0.3 microM), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP-ribose in the taenia coli. These potentiations were sensitive to 8-phenyltheophylline (5 microM). 6. Reactive blue 2, a P2Y-purinoceptor antagonist, antagonized the inhibitory responses of ADP-ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline.7. In the presence of the potassium channel blocker, apamin (0.3 microM), the inhibitory responses of ADP-ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8-PT blocked the residual responses of ADPribose.8. The P2-purinoceptor antagonist, suramin (500 microM), antagonized responses to ATP and ADP-ribose,but not adenosine. Further addition of 8-PT antagonized the residual responses to ADP-ribose, but not to ATP.9. It is concluded that ADP-ribose has a mixed pharmacological profile, evoking both PI (A2)-purinoceptor-mediated responses and P2Y-purinoceptor-mediated responses, while being inert at P2Xpurinoceptors.It is suggested that ADP-ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P2Y-purinoceptor.
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PMID:Activation of P1- and P2Y-purinoceptors by ADP-ribose in the guinea-pig taenia coli, but not of P2X-purinoceptors in the vas deferens. 142 86

The characteristics and distribution of [3H] alpha,beta-methylene ATP ([3H] alpha,beta-MeATP, a radioligand for P2x-purinoceptors) binding sites in the urinary bladder of rat, guinea-pig and rabbit were examined. Autoradiographic localization of [3H] alpha,beta-MeATP binding sites was also carried out on the urethra of the three species. Receptor binding assay showed that the rat bladder possesses the highest density of specific binding sites, followed by rabbit and guinea-pig bladder. Semi-quantitative analysis of autoradiograms showed that the grain densities in the bladders of rat, guinea pig, and rabbit were parallel to those obtained from receptor binding assay. The grain densities were greatly reduced in the presence of beta,gamma-methylene ATP (beta,gamma-MeATP). No significant specific binding was detected in the smooth muscle of rat and guinea-pig urethra, while a very low level of specific binding was observed in the rabbit urethra. Differences of grain densities in different regions (dome, body, and trigone) of the same bladder were also observed, but they were not as remarkable as those between species. The results of this study demonstrate species differences of P2X-purinoceptor densities in the urinary bladder, which may reflect differing degrees of purinergic neurotransmitter control of the bladder detrusor muscle.
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PMID:Species differences in characteristics and distribution of [3H] alpha,beta-methylene ATP binding sites in urinary bladder and urethra of rat, guinea-pig and rabbit. 152 55

The effect of external ATP on both the membrane potential and the transmembrane current of the thyroid cell line FRTL-5 has been investigated in the patch-clamp whole-cell recording configuration. In the resting situation the membrane potential is around -70 mV and the membrane acts like a K(+)-sensitive electrode. Application of ATP at concentrations higher than 1 microM elicited an increase in Cl- conductance, responsible for a membrane depolarization which could be blocked by preincubation with the P2-antagonist quinidine. Chelation of intracellular Ca2+ also blocked the ATP induced changes in membrane potential and Cl- current. Intracellular perfusion with inositol trisphosphate (IP3) (50 microM) also stimulated a Cl- current which mimicked the response induced by ATP. ATP is able to initiate a response in the absence of extracellular Ca2+, but also opens a Ca(2+)-influx pathway, as demonstrated by a secondary response upon Ca2+ readmission in the external medium, in the continued presence of ATP. ADP and ATP gamma S were able to mimic the ATP response, whereas AMP and adenosine were unable to elicit a Cl- current. The P2X receptor agonist alpha,beta-methyleneATP was without effect as was the P2Y receptor agonist 2-methylthio ATP. We conclude that ATP is able to elicit a large IP3-mediated Ca(2+)-dependent Cl- current and membrane depolarization via a novel P2-type purinergic receptor.
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PMID:ATP activates a Ca(2+)-dependent Cl- current in the rat thyroid cell line, FRTL-5. 155 36

Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.
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PMID:Roles of P2-purinoceptors in the cardiovascular system. 164 96

We evaluated the contractile reactivity to various stimuli, and the content and release of noradrenaline (NA) from a non-vascular tissue, the vas deferens, isolated from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The concentration-contraction curves for NA in tissue from animals of two ages (10-25 weeks and 30-45 weeks) were shifted to the left in SHR as compared with in age-matched WKY, with significant differences at 1.0 and/or 10 microM of NA. Similarly, the amplitude of contraction produced by electrical stimulation at 4, 8 and 16 Hz in the tissue was much larger in SHR than in WKY. However, ATP (10-100 microM) evoked contractions of the tissue to a similar extent in both SHR and WKY. The electrically evoked contractions of vas deferens from both strains were inhibited by isoprenaline in an approximate dose-dependent and equipotent manner. The tissue NA content, determined by HPLC-ECD, was nearly same in both SHR and WKY. In addition, the same amount of NA was released from the vas deferens of both strains by electrical stimulation in the presence of 4-aminopyridine. The present findings indicate that the contractile response of vas deferens to stimulation of alpha 1-adrenoceptors, but not of beta-adrenoceptors or P2X-purinoceptors, is more pronounced in SHR than in WKY and that a response indicative of hypertension may also occur in non-vascular tissue as it does in vascular tissue.
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PMID:Hyperreactivity of alpha 1-adrenoceptors, but not of P2X-purinoceptors, in vas deferens of spontaneously hypertensive rats. 165 81


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