Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Video microscopy of isolated axoplasm from the squid giant axon permits correlated quantitative analyses of membrane-bounded organelle transport both in the intact axoplasm and along individual microtubules. As a result, the effects of experimental manipulations on both anterograde and retrograde movements of membrane-bounded organelles can be evaluated under nearly physiological conditions. Since anterograde and retrograde fast axonal transport are similar but distinct cellular processes, a systematic biochemical analysis is important for a further understanding of the molecular mechanisms for each. In this series of experiments, we employed isolated axoplasm of the squid to define the nucleoside triphosphate specificity for bidirectional organelle motility in the axon. Perfusion of axoplasm with 2-20 mM ATP preserved optimal vesicle velocities in both the anterograde and retrograde directions. Organelle velocities decreased to less than 50% of optimal values when the axoplasm was perfused with 10-20 mM UTP, GTP, ITP, or CTP with simultaneous depletion of endogenous ATP with hexokinase. Under the same conditions, TTP and ATP-gamma-S were unable to support significant levels of transport. None of the NTPs tested had a differential effect on anterograde vs. retrograde movement of vesicles. Surprisingly, several inconsistencies were revealed when a comparison was made between these results and nucleoside triphosphate specificities that have been reported for putative organelle motors by using in vitro assays. These data may be used in conjunction with data from well-defined in vitro assays to develop models for the molecular mechanisms of axonal transport.
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PMID:Nucleotide specificity for the bidirectional transport of membrane-bounded organelles in isolated axoplasm. 169 15

1. Vasoconstrictor responses of the isolated and perfused canine epicardial coronary artery to uridine 5'-triphosphate (UTP) were analysed pharmacologically. 2. At basal perfusion pressure, UTP induced vasoconstriction in a dose-related manner and the vasoconstriction was sometimes followed by a slight vasodilatation at large doses (more than 10 nmol). The rank order of potency for vasoconstriction was UTP = UDP > ATP > TTP > or = ITP >> UMP. At raised perfusion pressure by 20 mM KCl, the vasoconstriction was not changed and a small vasodilatation was induced at large doses. The rank order of potency for vasodilatation was induced at large doses. The rank order of potency for vasodilatation was ATP >> ITP > or = UDP > UTP > or = TTP. The maximal vasodilator response to UTP was much less than that to ATP. UMP did not induce vasodilatation. 3. The P2X receptor agonist and desensitizing agent alpha, beta-methylene ATP (1 microM) and the P2 receptor antagonist suramin (100 microM) inhibited the vasoconstrictor responses to ATP but not those to UTP and UDP. The P2 receptor antagonist reactive blue 2 (30 microM) did not inhibit the vascular responses to UTP. 4. UTP (200 microM) desensitized the vasoconstrictor responses to UTP, but not either the vasodilator responses to UTP or the vasoconstrictor responses to ATP and UDP. UDP (200 microM) did not desensitize the vascular responses to UTP. 5. Preincubating the UDP stock solution and arterial preparation with hexokinase (10 and 1 uml-1, respectively) did not change the vasoconstrictor responses to UDP. 6. The Ca channel blocker diltiazem (1 microM) inhibited the vasoconstrictor responses to UTP but not those to ATP and UDP. Incubation in a Ca(2+)-free solution containing 1 mM EGTA inhibited the vascular responses to ATP, UTP and UDP. 7. Removal of the endothelium by an intraluminal injection of saponin (1 mg) inhibited the vasodilator responses to UTP. Indomethacin, a cyclo-oxygenase inhibitor (1 microM), inhibited the vasodilator responses to UTP, but NG-nitro-L-arginine, a nitric oxide synthase inhibitor (300 microM), did not have an inhibitory effect. 8. The results suggest that (1) UTP induces vasoconstriction via UTP-preferring P2Y receptors on the smooth muscle and vasodilatation via receptors different from those mediating the vasoconstriction induced by UTP and mediating the vasodilatation by ATP on the endothelium, through mainly the release of prostacyclin in the canine epicardial coronary artery; (2) UDP induces vasoconstriction via UDP-preferring P2Y receptors; and (3) L-type Ca ion channels are involved in the vasoconstriction induced by UTP, but not in that induced by UDP.
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PMID:UTP induces vascular responses in the isolated and perfused canine epicardial coronary artery via UTP-preferring P2Y receptors. 942 7