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

Phencyclidine (PCP) abuse is reaching alarming proportions. PCP has recently been shown to induce hypertensive encephalopathies, microvascular cerebrovasospasm and acute intracerebral hemorrhage. Since we have shown in vitro that cerebral vasospasms induced by PCP could be completely reversed, or prevented, by use of organic calcium antagonists, we utilized a television microscope recording system to determine whether magnesium ions (Mg2+) could inhibit the ability of PCP to induce contraction of pial arterioles and its sequelae of microvascular damage. Administration of either MgCl2 or Mg aspartate HCl, i.a. or i.v. (1, 10, and 20 mumol/min), before or after administration of PCP produced dose-dependent inhibition (30-80%) of PCP-induced arteriolar spasms and the subsequent vascular damage. A variety of pharmacologic receptor antagonists and cyclooxygenase inhibitors failed to influence PCP-induced cerebrovasospasms. These data suggest that a naturally-occurring Ca2+ antagonist, viz. Mg2+, may be useful in the treatment of PCP intoxication and its cerebral vascular consequences.
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PMID:Magnesium ions prevent phencyclidine-induced cerebrovasospasms and rupture of cerebral microvessels: direct in-vivo microcirculatory studies on the rat brain. 236 50

The relaxant action of adenine nucleotides was studied in isolated rabbit trachealis to assess the presence of P2-purinoceptors in the airways, their cellular location, and pharmacologic properties. Strips of tracheal smooth muscle with intact epithelium were incubated in tissue baths and contracted with 1 microM acetylcholine. Over a dose range of 0.1 microM to 1 mM, ATP and ADP were significantly more potent than adenosine in relaxing tracheal smooth muscle. Significant relaxations were also elicited by AMP-PCP, AMP-CPP, and AMP-PNP, three ATP analogs stable to enzymatic hydrolysis to adenosine. In the absence of acetylcholine, neither ATP nor AMP-CPP exerted any contractile effect on the tracheal strips. In tissues selectively denuded of epithelium, ATP-, ADP-, and AMP-PCP-induced relaxations were markedly reduced. ATP-induced relaxation was also inhibited by the P2y-purinoceptor antagonist Reactive Blue 2 (RB2) (50 to 300 microM) and partially reduced by the cyclooxygenase inhibitor indomethacin (10 microM), whereas adenosine-induced relaxation was not significantly affected by these agents. These results suggest that ATP can induce smooth muscle relaxation in acetylcholine-contracted tracheal strips through a distinct P2-purinoceptor. This receptor appears to be located on the epithelium where its relaxant effect is mediated in part by release of one or more cyclooxygenase products. Additional relaxation at high ATP concentrations may occur through enzymatic hydrolysis of ATP to adenosine and interaction at P1-purinoceptors.
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PMID:Relaxation of rabbit tracheal smooth muscle by adenine nucleotides: mediation by P2-purinoceptors. 811 Apr 78

The effect of NMDA receptor antagonist phencyclidine (PCP) on expression of cyclooxygenase (COX)-2 mRNA in the rat brain was studied. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of COX-2 mRNA and heat shock gene hsp-70 mRNA, a marker of neuronal injury, in the retrosplenial cortex, in a dose-dependent manner. These results suggest that COX-2 may play a role in the neurotoxicity of NMDA receptor antagonists.
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PMID:Expression of cyclooxygenase-2 mRNA in rat retrosplenial cortex following administration of phencyclidine. 926 87

Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membrane potential (MMP), as measured by rhodamine 123 fluorescence in a flow cytometer. This effect was inhibited by several NMDA-receptor antagonists with the following rank order of potency: MK-801 > PCP > TCP > dextrorphan > dichlorokynurenic acid > D-AP5 > dextromethorphan. Neither spermine nor arcaine modified the NMDA-induced reduction in MMP, whereas ifenprodil and eliprodil inhibited this response in the micromolar range. The mechanism responsible for the alteration of MMP mediated by NMDA was studied. Mepacrine and dibucaine prevented the MMP reduction induced by NMDA, as did W13 (calmodulin antagonist). In contrast, this effect was not blocked by cyclooxygenase or lipooxygenase inhibitors, H7 (a protein kinase C inhibitor) or nitroarginine (nitric oxide synthase inhibitor). These data suggest a direct interaction between NMDA-receptor activation and arachidonic acid formation, and indicate that NMDA receptor-mediated effect on MMP could involve arachidonic acid.
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PMID:Modulation of neuronal mitochondrial membrane potential by the NMDA receptor: role of arachidonic acid. 944 14