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)

Oxygen consumption is pathologically dependent on oxygen delivery in ARDS and sepsis. We asked whether oxygen consumption is dependent on oxygen delivery in severe acute respiratory failure secondary to AIDS-related PCP. In five patients who had AIDS-related PCP, diffuse bilateral pulmonary infiltrates, no evidence of bacterial infection, and acute respiratory failure requiring mechanical ventilation with arterial oxygen tensions less than 75 mm Hg while breathing at least 50 percent oxygen, and PEEP greater than 10 cm H2O, we determined oxygen delivery and consumption by calculation from thermodilution cardiac output and arterial and mixed venous oxygen contents. Oxygen delivery was increased using transfusion of two units of packed red blood cells over one hour. Oxygen delivery increased 22 percent (638 +/- 204 to 778 +/- 201 ml/min.m2, p less than or equal to 0.006). Oxygen consumption increased 11 percent (134 +/- 34 to 149 +/- 29 ml/min.m2, p less than or equal to 0.02). The oxygen extraction ratio did not change. We conclude that similar to ARDS and sepsis, oxygen consumption may be pathologically dependent on oxygen delivery in patients who have severe acute respiratory failure secondary to AIDS-related PCP.
Chest 1990 Dec
PMID:Pathologic dependence of oxygen consumption on oxygen delivery in acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia. 224 89

Pneumocystis carinii (PCP) pneumonia is the most common pulmonary infection associated with the acquired immunodeficiency syndrome (AIDS). Patients at risk for PCP have defects in T lymphocyte function and include cancer and transplant patients who are on immune suppressing agents and corticosteroids. In West Virginia, PCP accounted for 53 percent of pulmonary infections in 144 cases of AIDS from 1984 to May 1990. Nationally, at least 100,000 cases of PCP are projected for the early part of this decade. Patients with PCP may present with non-specific symptoms. The chest X-ray frequently shows diffuse bilateral infiltrates but may have atypical features. Definitive diagnosis should be established using sputum staining and various bronchoscopic techniques. Trimethoprimsulfamethoxazole and IV pentamidine are the most efficacious agents for treatment, and monthly aerosolized pentamidine is recommended for prophylaxis. Further basic science and clinical research on the biology of the P. carinii and its response to treatment strategies in HIV and non-HIV related infections is urgently needed.
W V Med J 1990 Dec
PMID:Pneumocystis carinii pneumonia. 227 Jun 82

Ionic gradients imposed by choline Cl replacement of K methanesulfonate (Mes) at constant [K][Cl] product stimulate 45Ca efflux from skinned muscle fibers; a small, sustained Ca2+-insensitive efflux component, observed in EGTA, appears to grade a much larger Ca2+-dependent component responsible for contractile activation and is likely to reflect intermediate steps in excitation-contraction coupling. The present studies examined ATP-related effects on the Ca2+-insensitive stimulation. 45Ca efflux was measured on segments of frog semitendinosus muscle skinned by microdissection, with isometric force monitored continuously. The Ca2+-insensitive component was potentiated by quercetin, a flavonoid thought to inhibit the sarcoplasmic reticulum (SR) Ca pump by stabilizing a phosphorylated intermediate. Quercetin increased the stimulated net 45Ca release in the absence of EGTA, as expected from inhibition of reaccumulation, but its effectiveness in EGTA indicated potentiation of unidirectional efflux as such. Quercetin also increased unstimulated (control) 45Ca efflux in EGTA, to a smaller extent; potentiation appeared to be a function of efflux, with stimulation above control loss increased approximately 2.6-fold. ATP removal before stimulation, which led to rigor force and increased stiffness, prevented all quercetin effects in EGTA. ATP removal by itself inhibited ionic stimulation of the Ca2+-insensitive component, with little residual increase above the parallel control loss. Addition of the nonhydrolyzable ATP analogue AMP-PCP ([adenylyl-beta,gamma-methylene]diphosphate) (0.8 mM) after ATP removal gave similar results to ATP-free solution, which suggests that adenine nucleotide binding alone does not support stimulation by choline Cl. These results imply a fundamental role for ATP in the excitation of skinned fibers by imposed diffusion potentials; they also suggest that ATP regulates the SR Ca efflux channel, in a manner that could provide the positive feedback in Ca2+-dependent Ca release.
J Gen Physiol 1985 Dec
PMID:Excitation of skinned muscle fibers by imposed ion gradients. II. Influence of quercetin and ATP removal on the Ca2+-insensitive component of stimulated 45Ca efflux. 241 70

Phencyclidine (PCP) is a schizophrenomimetic drug of abuse. PCP binds with high affinity (apparent dissociation constant, KD less than 10(-6) M) to rat brain membranes and blocks, selectively, a voltage-gated, noninactivating K channel found in rat brain synaptosomes (presynaptic nerve terminals). Thus, it has been proposed that the high-affinity PCP receptor in brain is this K channel. Consistent with this hypothesis, we now show that several K channel blockers displace 3H-PCP from the rat brain receptor. Additionally, we have used a photolabile analog of PCP, m-azido-PCP (Az-PCP), to identify the brain PCP receptor/putative K channel. In the dark, Az-PCP bound reversibly to 2 classes of sites on rat brain synaptic membranes [KD = 0.14 +/- 0.01 microM (n = 5) for high-affinity binding, and KD = 255 +/- 55 microM for low-affinity binding]. Competitive binding studies between Az-3H-PCP and nonlabeled PCP analogs, and between Az-PCP and several tritiated PCP analogs, indicated that the high-affinity Az-PCP binding site is the high-affinity PCP receptor. Several amino-pyridines (APs) and tetraalkylamines (TAAs), which are known to block K channels in excitable cells, were also found to displace 3H-PCP from its high-affinity binding site on rat brain synaptic membranes. The rank order of potency for displacement of 3H-PCP from this site for the APs was 4-AP approximately equal to 3,4-diAP greater than 2-AP much greater than 3-AP; for the TAAs it was TBA greater than TEA much greater than TMA (the tetra-butyl, ethyl, and methyl amines, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
J Neurosci 1986 Dec
PMID:m-Azido-phencyclidine covalently labels the rat brain PCP receptor, a putative K channel. 243 4

We studied the effects of phencyclidine (PCP) on the transient and delayed outward K+ currents recorded from spinal cord neurons grown (10-20 days) in cell culture. Sodium channels were blocked with tetrodotoxin (1 microM) and solutions containing low calcium concentrations in the presence of Mg2+ or Co2+ (5 mM) were used to reduce Ca2+ currents. PCP decreased the amplitude and prolonged the decay phase of the action potentials recorded at a holding potential of -70 mV. PCP (0.1-0.5 mM) was more effective than tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in reducing both transient and delayed currents. The amplitude of the transient current during control experiments was always larger than that of the delayed current. It appeared that 4-AP (5 mM) was more potent in blocking the transient current, while TEA (10 mM) modified the delayed current more effectively. Both currents were also reduced by about 10% when the cell soma was perfused with Co2+. This suggested that a small fraction of the total outward current is a Ca2+-activated K+ current. The PCP-induced blockade of K+ currents in central neurons coupled with the profound synaptic effects of the drug may provide the basis for explaining the psychopathology of this hallucinogenic agent.
Brain Res 1987 Dec 08
PMID:Phencyclidine blocks two potassium currents in spinal neurons in cell culture. 244 18

The effects of three irreversible anticholinesterase agents, echothiophate (217MI), tertiary methylamine analog of 217MI (217AO) and Tetram, on end plate currents (e.p.c.s) of Rana pipiens cutaneous pectoris muscle were studied using electrophysiological techniques. All three compounds (217MI, 1-10 microM; 217AO, 1-25 microM; and Tetram, 1-50 microM) decreased the rate of e.p.c. decay (alpha) to the same extent as neostigmine (10 microM), a reversible anticholinesterase agent. Decay remained a single exponential at all membrane potentials. 217MI and its derivatives greatly reduced the normal voltage dependence of alpha represented by the slope (H = mV-1) of log alpha vs. membrane potential, in contrast to neostigmine which had no effect on H. Suppression of Ach release by the addition of 4 mM Mg++ to end-plates did not alter the reduction of H by 217AO indicating that the anticholinesterase-induced decrease in H is not simply due to an increased interaction between Ach and its receptors. Additionally, the pretreatment of end-plates with methanesulfonyl fluoride, also an irreversible cholinesterase agent, did not modify the effects of 217AO and Tetram on H. 217MI and its derivatives, at low concentrations which altered H, did not affect [3H]PCP or [125I]alpha-bungarotoxin binding to Torpedo californica Ach receptor-rich membranes. It is concluded that these agents alter H by an effect on the Ach receptor ion channel complex unrelated to either esterase inhibition or channel block.
J Pharmacol Exp Ther 1989 Dec
PMID:Echothiophate and cogeners decrease the voltage dependence of end-plate current decay in frog skeletal muscle. 248 Oct 33

7-Chlorokynurenic acid (7-Cl KYNA) has been reported to attenuate N-methyl-D-aspartate (NMDA) receptor functioning by a potent and selective inhibitory action mediated at the strychnine-insensitive glycine recognition site of the NMDA complex. Here we report that 7-Cl KYNA dose-dependently inhibits [3H]MK-801 binding to the PCP receptor, and that this effect is reversed by addition of glycine. Since [3H]MK-801 binding is a measure of channel activation, our results are consistent with the hypotheses that 7-Cl KYNA exerts its NMDA receptor antagonism by acting at the glycine site, and that activation of the glycine site is required for NMDA channel activity to occur.
Brain Res 1989 Dec 18
PMID:Glycine reverses 7-chlorokynurenic acid-induced inhibition of [3H]MK-801 binding. 255 30

Female Sprague-Dawley rats prepared with chronic i.v. cannulas and/or cerebrocortical electrodes were administered sequentially increasing doses of phencyclidine (PCP, 0.1-6.4 mg/kg/injection), (+)-SKF-10,047 [(+)-N-allynormetazocine] (0.4-25.6 mg/kg/injection) or MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate] (0.01-0.64 mg/kg/injection). Effects on overt behavior, cortical EEG power spectra, locomotor activity and rotarod performance were assessed. Quantitative EEG spectral parameters (peak, mean and edge frequency; total and relative power; time domain descriptors mobility and complexity) were analyzed from the global frequency range of 1 to 50 Hz. Increasing doses of each drug produced increases in EEG spectra power from 1 to 50 Hz which was associated with a slowing of the peak frequency. PCP and MK-801 produced decreases in the mean frequency, mobility and edge frequency whereas (+)-SKF-10,047 produced increases in these spectral parameters. Moreover, (+)-SKF-10,047 increased complexity whereas MK-801 decreased complexity and PCP did not change this parameter. Total spectral power from 20 to 50 Hz was increased by (+)-SKF-10,047 and PCP, but was not changed by MK-801. Each drug increased spontaneous locomotor activity. At the highest doses, PCP and MK-801 decreased activity whereas (+)-SKF-10,047 was lethal. Each drug disrupted rotarod performance. The rank order of potency for each effect was: MK-801 greater than PCP greater than (+)-SKF-10,047. The data indicate that subtle differences in the effects of these drugs can be detected using EEG power spectral analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1989 Dec
PMID:Comparative electroencephalographic and behavioral effects of phencyclidine, (+)-SKF-10,047 and MK-801 in rats. 255 12

The development of N-(1-[2-thienyl]-cyclohexyl)[3H]piperidine [( 3H]TCP) binding to phencyclidine (PCP) receptors in both brain homogenates and slices has been investigated in the rat. The specific binding sites for [3H]TCP in the homogenate were already detected at prenatal stages and steadily increased after birth. A similar developmental pattern was seen in the autoradiography of the [3H]TCP binding to the brain slice in which the distribution of the binding in the young is more homogeneous than that in adult. There was an increase in the Bmax without changes in the Kd of the [3H]TCP binding and there was no change in inhibition of the binding by TCP, PCP and D-(-)-2-amino-5-phosphonovalerate during postnatal maturation. These findings suggest an increase in the density with no change in the affinity of PCP receptors and the absence of a change in the interaction between the PCP and N-methyl-D-aspartate receptors in the developing rat forebrain.
Neurosci Lett 1989 Dec 15
PMID:Embryonic and postnatal development of N-(1-[2-thienyl]cyclohexyl)[3H]piperidine binding sites in rat forebrain homogenates and slices. 255 72

Drug abuse is on the rise in Mississippi. Treatment centers across the state report significant increases in substance abuse cases. Consequently, family physicians must have the most current, accurate information available and the skills with which to treat either an acute crisis or the chronic problems related to drug abuse. The authors present an overview of the clinical presentations and management of some of the most widely used designer drugs: crack, ecstasy and PCP.
J Miss State Med Assoc 1989 Dec
PMID:Update on street drugs in Mississippi. 261 25


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