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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In isolated, constant-pressure perfused rat kidneys at basal vascular tone, injected P2 purinoceptor agonists evoked vasoconstriction (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ATP > ADP = UTP). In kidneys with raised tone, the nucleotides produced vasodilatation at low doses (2-methylthio ATP > ADP = ATP = ATP-gamma-S > UTP; alpha, beta-methylene ATP and beta, gamma-methylene ATP, inactive), and constriction at high doses (alpha, beta-methylene ATP > beta, gamma-methylene ATP > ATP-gamma-S > 2-methylthio ATP > ADP = ATP > UTP). Removal of the endothelium abolished the dilator responses to the agonists. NG-Nitro-L-arginine methylester (L-NAME, 5 x 10(-5) M) abolished vasorelaxation in response to 2-methylthio ATP, a response which could be restored by additional L-arginine (3 x 10(-3) M). Both vasodilatation and constriction due to the nucleotides remained unaffected by indomethacin (3 x 10(-6) M), S-(p-nitrobenzyl)-6-thioinosine (3 x 10(-5) M) and 8-phenyltheophylline (3 x 10(-6) M). Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 1-3 x 10(-6) M), inhibited vasoconstriction caused by alpha, beta-methylene ATP, 2-methylthio ATP and UTP, but not by ATP. Suramin (3 x 10(-5) M) caused a rightward shift of the dose-response curves for constriction caused by alpha, beta-methylene ATP (27-fold) and 2-methylthio ATP (5-fold), whereas the ATP curve was shifted to the left (20-fold). With Evans blue (10(-5) M), vasodilatation due to the nucleotides was abolished and the dose-response curves for vasoconstriction caused by ATP and UTP were shifted left more than 100-fold, the effect to both could not be antagonized by PPADS (3 x 10(-6) M). These results suggest: (1) the different rank orders of P2 purinoceptor agonist potencies for constrictor and dilator responses in perfused rat kidney are consistent with mediation via P2x and P2Y purinoceptors, respectively; (2) P2X purinoceptors, selectively sensitive to blockade by PPADS, are located on vascular smooth muscle; (3) endothelial P2Y purinoceptor stimulation results in vasodilatation involving NO synthesis but not release of prostanoids; (4) Evans blue, which appears to combine selective P2Y purinoceptor blockade and strong inhibition of ecto-nucleotidases, potentiates vasoconstriction in response to the degradable nucleotides, ATP, 2-methylthio ATP and UTP; (5) additionally, Evans blue unmasks a PPADS-insensitive P2U purinoceptor where the nearly equipotent nucleotides, ATP and UTP, can produce vasoconstriction.
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PMID:Characterization of vascular P2 purinoceptors in the rat isolated perfused kidney. 881 26

1. In the isolated aorta of the frog, Rana temporaria, adenosine concentration-dependently, endothelium-independently relaxed adrenaline pre-constricted vessels. None of the adenosine analogues including D-5'-(N-ethylcarboxamide) adenosine (NECA), R- and S-N6-(2-phenylisopropyl) adenosine (R-and S-PIA) and 2-chloroadenosine (2-CA), or the more selective A1, A2 and A3 agonists cyclopentyladenosine (CPA), CGS 21680 and N6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide (IB-MECA) respectively, had any effect. 2. The non-selective adenosine antagonist, 8-p-sulphophenyl-theophylline (8-pSPT; 30 microM) failed to inhibit adenosine relaxations, as did NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mM) and indomethacin (30 microM). 3. Adenosine 5'-triphosphate (ATP), alpha, beta-methylene ATP (alpha, beta-MeATP), beta, gamma-methylene ATP (beta, gamma-MeATP), 2-methylthio ATP (2-MeSATP) and uridine 5'-triphosphate (UTP) all concentration-dependently contracted the frog aorta. ATP and alpha, beta-MeATP were equipotent and more potent than UTP and beta, gamma-MeATP; 2-MeSATP had little activity. 4. The P2-purinoceptor antagonist, suramin (0.1 mM) inhibited contractions to alpha, beta-MeATP but not to ATP. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 30 microM) also inhibited contractions to alpha, beta-MeATP but not to ATP. Contractions to ATP were, however, inhibited by indomethacin (30 microM). 5. In conclusion, in the frog aorta there appears to be a novel subclass of P1-purinoceptor mediating vasodilatation, although like the A3 subclass it is not blocked by methylxanthines; a P2-purinoceptor mediates vasconstriction which resembles a P2x subtype, based on the agonist potency of alpha, beta-MeATP being more potent than 2-MeSATP (UTP has moderate activity) and PPADS is an effective antagonist. There is no evidence for the presence of a P2y-purinoceptor, mediating vasodilatation, in this preparation.
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PMID:The effects of purine compounds on the isolated aorta of the frog Rana temporaria. 885 4

1. The aim of this study was to characterize P2 receptors in the arterial vascular bed of human perfused placental cotyledons. Vasoconstrictor responses to bolus injections of purine and pyrimidine nucleotides were tested at basal tone, and vasodilator responses in preparations with tone raised by perfusion with prostaglandin F2alpha (PGF2alpha; 10-50 nM). 2. At basal tone, bolus injections of the P2X-selective agonist alpha,beta-methylene ATP (alpha,beta-meATP; 0.5-500 nmol) elicited dose-dependent vasoconstriction. ATP (0.005-5 micromol) also elicited dose-dependent vasoconstriction, but was less potent than alpha,beta-meATP. Vasoconstriction was also elicited by other nucleotides, but only at the highest dose tested (5 micromol): UTP > CTP = ITP (n = 6). GTP and TTP did not cause vasoconstriction. 3. Constrictor responses to bolus injections of alpha,beta-meATP were resistant to desensitization and were not significantly affected when carried out in the presence of 1 microM alpha,beta-meATP added to the perfusate. However, responses to bolus injections of alpha,beta-meATP were partially blocked by perfusion with 10 microM alpha,beta-meATP. In contrast, responses to ATP and UTP were unaffected by 10 microM alpha,beta-meATP. The P2X receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 and 100 microM) had no significant effect on vasoconstriction mediated by alpha,beta-meATP and ATP. 4. Removal of the endothelium had no significant effect on constrictor responses to alpha,beta-meATP, ATP and UTP. Inhibition of nitric oxide (NO) synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 microM) had no significant effect on vasoconstriction to ATP and alpha,beta-meATP. 5. In preparations with tone raised with PGF2alpha (10-50 nM) vasodilatation was elicited by nucleotides with the following order of potency: 2MeSATP = ADP >> ATP > UTP > CTP = GTP = ITP = TTP. pD2 values were: 2MeSATP, 10.03+/-0.26 (n=7); ADP, 9.97+/-0.40 (n=5); ATP, 8.89+/-0.18 (n=7); UTP, 7.79+/-0.35 (n=7). Maximal responses to 2MeSATP and ADP were similar and were approximately 40% greater than maximal responses to ATP and UTP. 6. Vasodilator responses to nucleotides were abolished by L-NAME (100 microM) and by removal of the endothelium. 7. In conclusion, contractile responses mediated by alpha,beta-meATP and ATP in human placental smooth muscle are resistant to desensitization and insensitive to PPADS and, thus, show a dissimilar pharmacological profile to the classic smooth muscle P2X1 receptor. There may be two subtypes of smooth muscle P2 receptor based on differential antagonism of alpha,beta-meATP and ATP with alpha,beta-meATP. A smooth muscle P2 receptor mediates vasoconstriction to UTP, and may indicate a further subtype. Endothelium-dependent, NO-dependent, vasodilatation to 2MeSATP and ADP may be mediated by P2Y1 receptors, while endothelial P2Y2 receptors are likely to mediate NO-dependent relaxation to ATP and UTP.
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PMID:Characterization of P2 receptors for purine and pyrimidine nucleotides in human placental cotyledons. 924 47

1. Nitric oxide (NO) is known from previous studies to be the principle transmitter in NANC inhibitory nerves supplying the hamster urethra. However, the identity of the cotransmitter(s) responsible for the responses remaining following block with L-NG-nitroarginine methyl ester (L-NAME) is not known. 2. Electrical field stimulation (EFS) of circular strips of hamster proximal urethra precontracted with arginine vasopressin (AVP 10(-8) M), and in the presence of phentolamine (10(-6) M), propranolol (10(-6) M) and atropine (10(-6) M), caused frequency-dependent relaxation, which was attenuated by suramin (10(-4) M) and reactive blue 2 (RB2; 2 x 10(-4) M), but not by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by the vasoactive intestinal polypeptide (VIP) antagonist, [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, (5 x 10(-7)-10(-6) M). In the presence of indomethacin (10(-6) M) frequency-dependent relaxations to EFS were enhanced, particularly at the lower frequencies of stimulation. EFS-induced relaxation was blocked by tetrodotoxin (10(-6) M), indicating its neurogenic origin. 3. Exogenous ATP (10(-7)-10(-3) M) produced concentration-related relaxations which were attenuated by the P2-purinoceptor antagonists suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not by PPADS (10(-4) M). ATP-induced relaxations were also reduced significantly by indomethacin (10(-6) M). The inhibitory responses to ATP were urothelium- and NO-independent, since they were not affected by either removal of urothelium or by L-NAME (10(-4) M). 4. Exogenous VIP (10(-9)-10(-7) M) induced concentration-related relaxations which were not affected by urothelium removal, L-NAME (10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (3 x 10(-7)-10(-6) M). Nevertheless, suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not PPADS (10(-4) M) antagonized the VIP-induced relaxant responses. Calcitonin gene-related peptide (CGRP: 10(-9)-10(-7) M) was devoid of any effect or only elicited a small relaxant response in AVP-precontracted strips. 5. Exogenous prostaglandin E2 (PGE2; 10(-9)-3 x 10(-6) M) and the NO donor, sodium nitroprusside (SNP; 10(-8)-3 x 10(-5) M) elicited concentration-related relaxations on the hamster proximal urethra which were not attenuated by suramin (10(-4) M), RB2 (2 x 10(-4) M), or by PPADS (10(-4) M), indicating a specific inhibitory effect of the antagonists used. 6. In summary, these results are consistent with the view that ATP is an inhibitory transmitter released from inhibitory nerves supplying the NANC relaxation of hamster proximal urethra. The relaxant effect of ATP is NO- and urothelium-independent. The present study did not demonstrate whether VIP is released from parasympathetic nerves during EFS, since both alpha-chymotrypsin and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP were ineffective on neurogenic responses.
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PMID:ATP and vasoactive intestinal polypeptide relaxant responses in hamster isolated proximal urethra. 972 Jul 75

The effect of ATP in human and rabbit corpus cavernosum (CC) smooth muscle was investigated. Strips of human CC were vertically mounted in an organ bath and the tonic tension was recorded. ATP (0.1-3 mM) induced a concentration-dependent relaxant effect, with a pD2 value of 3.01+/-0.3. The purine-induced relaxation was not affected by L-NAME (100 microM). In rabbit CC, ATP also induced a concentration-dependent relaxation, which was not influenced by L-NAME or by indomethacin (3 microM), with a pD2 value of 3.1 +/-0.4. The ATP-induced relaxant effect in rabbit CC was increased by both the inhibitor of adenosine reuptake, dipyridamole (3 microM) and by the inhibitor of adenosine deaminase, EHNA (0.3 microM). Moreover CGS 15943 (3 microM), an A2a adenosine antagonist, reduced the ATP-induced relaxation. UTP was not able to produce relaxation. The two ATP analogues 2-methylthioATP and alpha,beta-methylene ATP were able to induce relaxation in rabbit CC, with the following order of potency: 2-methylthioATP > ATP > alpha,beta-methylene ATP thus suggesting a role for P2y receptors. However, reactive blue (500 microM), an unspecific P2y antagonist, did not modify the ATP relaxant response. The inhibition of phospholipase C by U73122 (3 microM) and of the endoplasmic reticulum Ca2+ATPase by thapsigargin (1 microM) did not modify the ATP-induced relaxation. The P2x specific antagonist PPADS (30 microM) and suramine (500 microM) were not able to modify the ATP relaxation either in the absence or presence of CGS 15943 (3 microM). These results confirm that ATP acts as a potent and NO-independent relaxant agent of human and rabbit CC. Our findings also show that the ATP effect is partially attributable to the metabolic breakdown of ATP to adenosine, which acts through A2a receptor stimulation, but is also due to a direct stimulation of P2 receptors that are different from the classical P2y and P2X receptor subtypes for ATP.
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PMID:Studies on the mechanisms involved in the ATP-induced relaxation in human and rabbit corpus cavernosum. 1003 32

In isolated mesenteric arteries of rats, dose-dependent increase in perfusion pressure by adenosine 5'-triphosphate (ATP, 0.1 approximately 3000 nmole) diminished with age. ATP responses of both 4- and 32-week-old rats were enhanced by indomethacin (5 microM), and further by the combination of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME, 5 microM). The enhancement with each of the treatments was less in 32-week-old rats than that in 4-week-old rats, and there was no enhancement in 75-week-old rats. The ATP response was enhanced by removing the endothelium only in 4-week-old rats. The constrictions in response to ATP (1000 nmole) in both 4- and 32-week-old rats were equally enhanced by reactive blue 2 (30 micromole) and were inhibited by pyridoxal-phosphate-6-azophenyl-2',4-disulphonic acid (PPADS, 30 microM) and alpha, beta-methylene ATP (alpha, beta-mATP, 100 nmole) to a similar extent. The increased tone which was produced by the perfusion with physiological solution containing 100 mM potassium chloride was greater in older animals. This age-related change in the vascular tone disappeared when the responses were potentiated by L-NAME. These results demonstrate that in rat mesenteric arteries, ATP-induced constriction decreases with age. The age-related decline of vasoconstriction is not likely to arise from the changes in the contractility of smooth muscle, from the counterbalancing regulation by the endothelium, or from the cooperation of P2 purinoceptor subtypes. The density of purinoceptors and some post-receptor signal transduction mechanisms in the vascular smooth muscle cells may change with age. The enhanced ATP response might have special physiological significance in rats during development.
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PMID:Age-related changes in adenosine 5'-triphosphate-induced constriction of isolated, perfused mesenteric arteries of rats. 1022 82

The role of nitric oxide (NO) and ATP in the regulation of nonadrenergic, noncholinergic (NANC) inhibitory transmission in the pylorus remains unclear. In the presence of atropine and guanethidine, electric field stimulation induced NANC relaxations in a frequency-dependent manner (1-20 Hz) in the rat pylorus. NANC relaxations were significantly inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M). P(2X) purinoceptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 3 x 10(-5) M) and P(2Y) purinoceptor antagonist reactive blue 2 (2 x 10(-5) M) had no effect on NANC relaxations. However, the combined administration of L-NAME and PPADS, but not reactive blue 2, evoked greater inhibitory effects on NANC relaxation than that evoked by L-NAME alone. alpha-Chymotrypsin and vasoactive intestinal polypeptide antagonist did not affect NANC relaxations. ATP (10(-5)-10(-3) M) and P(2X) purinoceptor agonist alpha, beta-methyleneadenosine 5'-triphosphate (10(-7)-10(-5) M), but not P(2Y) purinoceptor agonist 2-methylthioadenosine 5'-triphosphate (10(-7)-10(-5) M), induced muscle relaxations in a dose-dependent manner, and relaxations were significantly reduced by PPADS and unaffected by TTX. These studies suggest that NO and ATP act in concert to mediate NANC relaxation of the rat pylorus. ATP-induced relaxation appears to be mediated by P(2X) purinoceptors located on smooth muscle cells.
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PMID:Nitrergic and purinergic regulation of the rat pylorus. 1100 61

In the isolated Agama lizard aorta, acetylcholine (ACh; 3 nM-100 microM), noradrenaline (NA; 30 nM-0.3 mM), adrenaline (Adr; 30 nM-300 microM), adenosine 5'-triphosphate (ATP; 30 nM-1 mM), alpha,beta-methylene ATP (alpha,beta-meATP; 10 nM-10 microM), beta,gamma-methylene ATP (beta,gamma-meATP; 0.1-300 microM), 2-methylthio ATP (2-meSATP; 30 nM-30 microM) and high concentrations of uridine triphosphate (UTP; 1 microM-1 mM), all produced constriction. The P2 receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 30 microM), suramin (0.1 mM) and Reactive blue 2 (30 microM) all raised vascular tone and could not be utilized and the antagonist 2'-O-(trinitrophenyl) ATP (TNP-ATP; 0.1 microM) had no effect on responses to the ATP analogues. alpha,beta-MeATP (3 microMx3) desensitised responses to alpha,beta-meATP (10 microM) and beta,gamma-meATP (0.3 mM), but not to ATP (0.3 mM) or 2-meSATP (30 microM). On pre-constricted aorta (EC50 concentration of either ACh or Adr), adenosine (1 microM-1 mM), the A1-selective agonist N6-cyclopentyl adenosine (CPA; 1-300 microM) [but not the A2- and A3-selective agonists CGS 21680 and IB-MECA respectively (both up to 30 microM)] and sodium nitroprusside (10 nM-100 microM) produced vasodilatation. Adenosine vasodilatation was antagonised by 8-p-sulfophenyl-theophylline (8-pSPT; 30 microM) but not by N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.1 mM). ATP (up to 0.3 mM), 2-meSATP (up to 10 microM) and UTP (up to 1 mM) were not vasodilators. In summary, A1 receptors mediating relaxation and excitatory P2X1 receptors were identified in the smooth muscle of the lizard aorta. However, in contrast to mammalian aorta, P2Y receptors on endothelial cells mediating vasodilatation via nitric oxide do not appear to be present.
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PMID:Identification of P1 and P2 purinoceptors in the aorta of the lizard (Agama sp.). 1125 14

Post-transplantation thrombosis may occur in donor segments of iliac arteries and livers following surgical removal and storage in University of Wisconsin (UW) solution for transplantation. We have previously suggested that purine receptors are vulnerable to denaturation after UW storage. The aims of the present study were to determine what particular subtypes of purine P2Y receptors in rabbit thoracic aorta deteriorate after 8 days of UW storage by studying vascular reactivity to acetylcholine, ATP, 2MeSATP and UTP. Ring segments of aortae from male New Zealand White rabbits were mounted upon fine-wire myographs and vasodilatation to the above agents tested on fresh tissue, and after 8 days of UW storage. Vasodilatation to ATP was attenuated by 100 microM L-NAME in fresh tissue suggesting that the relaxant response was, in part, due to nitric oxide (NO). P2Y-mediated relaxation to ATP was significantly attenuated by UW storage and cholinergic responses were not. This attenuated relaxation to ATP was not further attenuated by L-NAME, suggesting a loss of the NO-dependent mechanism. De-endothelialisation indicated that UTP-mediated vasorelaxation, via P2Y(2) receptors, was endothelium-dependent. Any residual endothelium-independent relaxation to UTP was abolished by UW storage and endothelium-dependent UTP relaxation was reduced to the same level as that seen in fresh, de-endothelialised tissue. In contrast responses to 2MeSATP, via P2Y(1) receptors, were predominantly endothelium-independent and were only partially attenuated by UW storage. Responses to pyridoxalphosphate-6-azophenyl-2('),4(')-disulphonic acid (PPADS) and L-NAME suggested that vasorelaxation to 2MeSATP and UTP was mediated by P2Y(1) and P2Y(2) receptors, respectively. It is therefore concluded that UW storage predominantly decreases P2Y(2) receptor-mediated vascular reactivity.
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PMID:Cold storage of rabbit thoracic aorta in University of Wisconsin solution attenuates P2Y(2) purine receptors. 1215 Dec 64

Non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmission has been an area of intense interest in gut motor physiology, whereas excitatory NANC neurotransmission has received less attention. In order to further explore excitatory NANC neurotransmission, we performed conventional intracellular recordings from guinea-pig taenia caeci smooth muscle. Tissue was perfused with oxygenated Krebs solution at 35 degrees C and nerve responses evoked by either oral or aboral nerve stimulation (NS) (4 square wave pulses, 0.3 ms duration, 20 Hz). Electrical activity was characterized by slow waves upon which one to three action potentials were superimposed. Oral NS evoked an inhibitory junction potential (IJP) at either the valley or peak of the slow wave. Application of nifedipine (1 microM) abolished slow waves and action potentials, but membrane potential flunctuations (1-3 mV) and IJPs remained unaffected. Concomitant application of apamin (300 nM), a small-conductance Ca(2+)-activated K(+) channel blocker, converted the IJP to an EJP that was followed by slow IJP. Further administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 200 microM), a nitric oxide synthase inhibitor, abolished the slow IJP without affecting the EJP, implying that the slow IJP is due to nitrergic innervation. The EJP was abolished by tetrodotoxin (1 microM), but was not significantly affected by atropine (3 microM) and guanethidine (3 microM) or hexamethonium (500 microM). Substance P (SP, 1 microM) desensitization caused slight attenuation of the EJP, but the EJP was abolished by desensitization with alpha,beta-methylene ATP (50 microM), a P2 purinoceptor agonist that is more potent than ATP at the P2X receptor subtype, suramin (100 microM), a non-selective P2 purinoceptor antagonist, and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 microM) , a selective P2X purinoceptor antagonist. In contrast, the EJP was unaffected by MRS-2179 (2 microM), a selective P2Y(1) receptor antagonist. Aboral NS evoked an apamin- and l-NAME-sensitive IJP, but virtually no NANC EJP. These data suggest the presence of polarized excitatory purinergic neurotransmission in guinea-pig taenia caeci, which appears to be mediated by P2X purinoceptors, most likely the P2X(1) subtype.
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PMID:Excitatory purinergic neurotransmission in smooth muscle of guinea-pig [corrected] taenia caeci. 1567 92


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