Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The ontogeny of responses to purines and analogues of smooth muscle preparations was studied in rat duodenum and rat urinary bladder. 2. Responses to adenosine and to adenosine 5'-triphosphate (ATP) mediated by P1- and P2-purinoceptors respectively were present as early as postnatal day 2, the earliest day studied. 3. In rat bladder, adenosine was inhibitory and ATP and adenosine 5'-(beta, gamma-methylene) triphosphonate (AMP-PCP) were excitatory, acting on the P2X subtype of P2-purinoceptors. Adenosine was more potent in the neonate than in the adult, while the potency of the nucleotides initially increased with age but then declined, being highest between postnatal days 10 and 25. 4. In rat duodenum also, adenosine was inhibitory, its potency being less than the adult before day 15. 5. ATP at low concentrations was inhibitory in rat duodenum at every age studied and its potency increased with age, but higher concentrations of ATP (3 microM and above) were excitatory until day 15. Both relaxations and contractions were mediated by the P2Y subtype of P2-purinoceptors. These ATP-induced contractions were not inhibited by indomethacin (25 microM) or by tetrodotoxin (1 microM) and are therefore not due to prostaglandin synthesis or to ATP-induced release of transmitter substances from nerves. 6. These results show that responses to adenosine and to adenine nucleotides are present from birth and vary with age, and that the changes seen indicate a differential development for P1-, P2X- and P2Y-purinoceptors.
 ...
PMID:The ontogeny of purinoceptors in rat urinary bladder and duodenum. 220 6

Isopolar methylene phosphonate analogues of adenosine triphosphate (ATP) were synthesized and tested on the guinea-pig isolated taenia coli (where ATP causes relaxation) and urinary bladder (where ATP causes contraction), to see if restoration of the electronegativity of the methylene linkage would enhance pharmacological potency. The compounds used were the dichloromethylene and difluoromethylene analogues of adenosine 5'-(beta,gamma-methylene)triphosphonate (AMP-PCP), L-adenosine 5'-(beta,gamma-methylene)triphosphonate (L-AMP-PCP) and 2-methylthioadenosine 5'-(beta,gamma-methylene)-triphosphonate (2-methylthio-AMP-PCP). The order of potency of the analogues depended on the tissue, and was independent of the nature of the purine or ribose moieties. None of the analogues was degraded by ectonucleotidases on either tissue. In the taenia coli the order of potency for relaxation was difluoromethylene greater than or equal to dichloromethylene greater than methylene, and this reflected the order of electronegativity of the analogues. The isopolar analogues of L-AMP-PCP were inactive in the taenia coli. In the bladder the order of potency for contraction was difluoromethylene greater than or equal to methylene greater than dichloromethylene, suggesting that electronegativity is of lesser importance here. The isopolar analogues of L-AMP-PCP were active in this tissue. The differences between the two tissues in the order of potency for these non-degradable analogues supports suggestions that P2-purinoceptors in the taenia coli (P2Y) are different from those in the bladder (P2X). The isopolar analogues of L-AMP-PCP, like L-AMP-PCP itself, were selective agonists at the P2X-purinoceptor.
 ...
PMID:Pharmacological effects of isopolar phosphonate analogues of ATP on P2-purinoceptors in guinea-pig taenia coli and urinary bladder. 358 Jul 9

Glial cells are closely associated with synapses and are modulated by neurotransmitters released during synaptic transmission. At many synapses, ATP is released during synaptic transmission and is involved in cell-cell signaling. Since glial cells have purinoceptors, it is possible that ATP mediates synaptic neuron-glia signaling. This work aims at determining which types of purinoceptors are present on perisynaptic Schwann cells, the perisynaptic glial cells at the frog neuromuscular junction, and test their sensitivity to endogenous purines by monitoring the relative changes of intracellular Ca2+. Local application of ATP induced the release of Ca2+ from internal stores. Adenosine induced Ca2+ responses that were blocked by A1 receptor antagonists and mimicked by an A1 receptor agonist and were caused by the release of Ca2+ from internal stores via a pertussis toxin-sensitive G-protein. A2 receptor antagonists had no effect on Ca2+ responses induced by adenosine. Me-S-ATP, an ATP analog, triggered Ca2+ release from internal stores via a pertussis toxin-sensitive G-protein, consistent with the activation of P2Y receptors. L-AMP-PCP, another ATP analog, induced Ca2+ entry mainly through L-type Ca2+ channels by a pertussis toxin-insensitive mechanism, consistent with the activation of P2X receptors. Blockade of adenosine receptors did not affect glial Ca2+ responses induced by nerve evoked transmitter release. However, blockade of ATP receptors reduced the size and increased the delay of the responses. Hence, purinoceptors are present on the perisynaptic Schwann cells and are activated by endogenous ATP released during synaptic transmission.
 ...
PMID:Purinergic receptors and their activation by endogenous purines at perisynaptic glial cells of the frog neuromuscular junction. 747 66

Six per cent of rat pheochromocytoma (PC12) cells extended neurites (processes greater than one cell diameter in length) in the presence of 300 microM extracellular GTP or 300 microM guanosine for 48 hr, compared to only 2.5% of cells in control cultures. In the presence of 40 ng/ml of 2.5S NGF, about 20-35% of PC12 cells had neurites after 48 hr, and the addition of 300 microM guanosine or GTP together with NGF synergistically increased the proportion of cells with neurites to 40-65%. GTP and guanosine also increased the average number of branches per neurite, from 0.6 in NGF-treated cultures to 1.2 (guanosine) or 1.5 (GTP). Neurites formed after exposure to NGF alone had axonal characteristics as determined by immunocytochemistry with antibody, SMI-31, against axonal-specific polyphosphorylated neurofilament epitopes. Neurites generated with the addition of both guanosine or GTP had the same characteristics. GTP probably did not exert its effects via the P2X or P2Y purinoceptors because the adenine nucleotides ATP, ATP gamma S, ADP beta S, and ADP, which are all agonists of these receptors, inhibited rather than enhanced, NGF-induced neurite outgrowth. UTP also enhanced the proportion of cells with neurites, although not to the same degree as did GTP. This may indicate activity through a P2U-like nucleotide receptor. However, the response profile obtained, GTP > UTP >> ATP, does not fit the profile of any known P2Y, P2X or P2U receptor. The poorly hydrolyzable GTP analogues, GTP gamma S and GDP beta s were also unable to enhance the proportion of cells with neurites. This implied that GTP may produce its effects through a GTP-specific ectoenzyme or kinase. This idea was supported by results showing that another poorly hydrolyzable analogue, GMP-PCP, competitively inhibited the effects of GTP on neurite outgrowth. GTP did not exert its effects after hydrolysis to guanosine since the metabolic intermediates GDP and GMP were also ineffective in enhancing the proportion of cells with neurites. Moreover, the effects of GTP and guanosine were mutually additive, implying that these two purines utilized different signal transduction mechanisms. The effects of guanosine were not affected by the nucleoside uptake inhibitors nitrobenzylthioinosine (NBTI) and dipyridamole, indicating that a transport mechanism was not involved. Guanosine also did not activate the purinergic P1 receptors, because the A2 receptor antagonists, 1,3-dipropyl-7-methylxanthine (DPMX) or CGS15943, and the A1 receptor antagonist, 1,3-dipropyl-8-(2-amino-4-chloro)xanthine (PACPX) did not inhibit its reaction. Therefore guanosine enhanced neurite outgrowth by a signal transduction mechanism that does not include the activation of the P1 purinoceptors. The enhancement of the neuritogenic effects of NGF by GTP and guanosine may have physiological implications in sprouting and functional recovery after neuronal injury in the CNS, due to the high levels of nucleosides and nucleotides released from dead or injured cells.
 ...
PMID:GTP and guanosine synergistically enhance NGF-induced neurite outgrowth from PC12 cells. 877 5

We evaluated the effects of increasing the viscosity (eta) in peritubular capillary perfusates (PCP; 20 mM HNaPO4--Ringer, pH 7.4) on proximal convoluted tubule (PCT) acidification. Micropuncture experiments were performed with simultaneous luminal and peritubular perfusion. Changes in pH of a 20 mM HNaPO4--Ringer (pH 7.4 at t = 0) droplet placed in PCT lumen were measured with H+-sensitive microelectrodes. By adding neutral dextran (molecular wt 300,000-400,000) to the PCP, eta was increased. The effect of 10(-5) M ATP added to normal-eta PCP was evaluated. High eta increased H+ flux (85 and 97% when eta was increased 20 and 30%, respectively, above the control value). This increase was abolished by adding the nitric oxide antagonist N(omega)-nitro-L-arginine (L-NNA; 10(-4) M) or the purinoreceptor antagonists suramin (10(-4) M) and reactive blue 2 (3 x 10(-5) M). Addition of 5 x 10(-3) M L-arginine to the peritubular perfusate overcame the inhibitory effect of L-NNA on high-eta-induced increase in H+ flux. ATP increased H+ flux (80%), and this effect was blocked by L-NNA. These results suggest that changes in eta can modulate proximal H+ flux, at least in part, through ATP-dependent nitric oxide release from the endothelial cells of the peritubular capillaries.
 ...
PMID:Peritubular fluid viscosity modulates H+ flux in proximal tubules through NO release. 1120 99