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)

In the present study, the authors found that, in Mg++-free buffer, N-methyl-D-aspartate (NMDA) was able to evoke the Ca++-dependent and tetrodotoxin-sensitive release of striatal acetylcholine (ACh), presumably via interaction with receptors on cholinergic interneurons. In Mg++-free buffer containing pargyline, NMDA also evoked a Ca++-dependent and tetrodotoxin-sensitive release of striatal [3H]dopamine (DA). Phencyclidine (PCP) and physiological concentrations of Mg++ (1.2 mM) also inhibited ACh release evoked by L-glutamate, L-aspartate and DL-homocysteate, but not ACh release evoked by the glutamate analogs quisqualate and kainate, suggesting that PCP is selective for the magnesium-sensitive, NMDA-preferring glutamate-aspartate receptor subtype. Comparison of PCP inhibition of NMDA-stimulated ACh and DA release with that produced by the competitive NMDA antagonist 2-amino-5-phosphonovalerate indicates that PCP is probably not altering release by a direct action on the NMDA recognition site. The ability of 2-amino-5-phosphonovalerate, but not PCP, to prevent desensitization of NMDA-induced ACh release is consistent with this interpretation. Binding studies did, however, reveal a reduction in the apparent affinity of the PCP binding site by high concentrations of NMDA. This may suggest an allosteric link between the PCP-sigma receptor and the NMDA-type glutamate-aspartate receptor. The receptors mediating excitatory amino acid-induced DA release were somewhat less selective than those on cholinergic neurons in their sensitivity to both Mg++ and PCP. Structure-activity-relationship studies suggested that the inhibition off ACh and DA release evoked by NMDA involves biding to the PCP-sigma receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1986 Sep
PMID:Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs. 287 74

A selective N-methyl-D-aspartate antagonist, DL-2-amino-5-phosphonovalerate, was found to produce PCP-like catalepsy, discriminative stimulus effects, and stereotyped operant responding in pigeons when administered intramuscularly. These results support the hypothesis that the behavioral effects of PCP-like drugs result at least in part from reduced neurotransmission at excitatory amino acid synapses utilizing N-methyl-D-aspartate preferring receptors.
Life Sci 1986 Sep 15
PMID:Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5-phosphonovalerate. 287 74

Phencyclidine (PCP) significantly reduces the apparent dissociation constant (KD) of the dihydropyridine (DHP) calcium channel antagonist, [3H]nitrendipine, in synaptosomal membranes of rat and mouse brain without significantly effecting the maximum binding capacity (Bmax). At an optimum concentration of PCP (10 microM) the apparent KD of [3H]nitrendipine was reduced from 178 +/- 9 pM to 112 +/- 9 pM in rat forebrain, a 58% increase in affinity. The structural derivatives of PCP, P-Br-PCP [1-[1-(4-bromo-phenyl-cyclohexyl)piperidine]], m-NH2-PCP [1-[1-(3-anilo)-cyclohexyl]piperidine], (+/-)-PCMP [1-(1-phenyl)-cyclo-hexyl-3-methylpiperidine] also increased the apparent affinity of [3H]nitrendipine in the following order, p-Br-PCP much greater than PCMP greater than PCP greater than m-NH2-PCP. Local anesthetics either reduced the apparent affinity of [3H]nitrendipine or had no effect. Kinetic analysis revealed that PCP both increased the microassociation rate constant and decreased the microdissociation rate constant of [3H]nitrendipine. The magnitude of this enhanced binding varied with the brain region studied; the greatest increase in apparent affinity of [3H]nitrendipine was observed in striatum, while no significant increase in affinity was observed in brainstem. In some brain areas, PCP was more effective in reducing the KD in crude homogenates than in washed tissue. PCP (10 microM) did not alter the KD of [3H]nitrendipine to rat cardiac tissue. Both Ca2+ and Mg2+ inhibited the effect of PCP, while monovalent ions were ineffective in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)
Naunyn Schmiedebergs Arch Pharmacol 1985 Sep
PMID:Phencyclidine increases the affinity of dihydropyridine calcium channel antagonist binding in rat brain. 293 50

Metaphit, a derivative of phencyclidine (PCP), irreversibly binds to PCP sites in rat brain homogenates. PCP-induced catalepsy in pigeons, which is a pharmacologically specific and stereoselective phenomenon, was used to study pharmacological consequences of the proposed covalent bonding of metaphit to PCP sites. Metaphit pretreatment increased the cataleptic effects induced by cumulative doses of PCP-type drugs (i.e., PCP, ketamine and m-amino PCP) and of drugs that have PCP-like actions (i.e., dexoxadrol, LY 154716 and cyclazocine). Metaphit did not affect pentobarbital-induced loss of righting, head-drop and eye closure. Metaphit itself induced a PCP-like catalepsy. Isobolographic analysis of the interactions between metaphit and PCP-like drugs suggested that metaphit potentiated the catalepsy-inducing effects of these drugs. The possibility that metaphit exerts its potentiating effects by inhibition of PCP biotransformation was evaluated by measuring plasma and brain concentrations of PCP after pretreatment with either metaphit or SKF-525A, an inhibitor of the enzyme systems involved in PCP biotransformation. SKF-525A, but not metaphit, increased brain levels of PCP. The results suggest that metaphit acts not as an antagonist of PCP but as a less-potent, long-acting, specific PCP-like agonist. Potentiation by metaphit of the cataleptic effects of chemically diverse drugs with PCP-like actions does not appear to be based on inhibition of the enzyme systems involved in metabolism of those drugs.
J Pharmacol Exp Ther 1985 Sep
PMID:Effects of metaphit, a proposed phencyclidine receptor acylator, on catalepsy in pigeons. 299 88

The anatomical localization of phencyclidine (PCP)/sigma-opiate receptors in rat brain was determined by quantitative light microscopy autoradiography using the new ligand N-(1-[2-thienyl]cyclohexyl) [3H]piperidine ([3H]TCP). TCP is a potent analog of PCP which possesses a higher affinity for PCP/sigma-opiate receptor than does PCP itself. The highest level of [3H]TCP binding was detected in the hippocampus. Intermediate levels were found in frontal cortex, striatum, amygdala and cerebellum. Specific [3H]TCP binding was undetectable in anterior commissure and corpus callosum. The distribution pattern of [3H]TCP binding sites is similar to the pattern obtained with [3H]PCP but more sharply defined. On the basis of its greater potency and specificity, [3H]TCP may prove superior to [3H]PCP as a molecular probe for the study of brain sigma opiate/phencyclidine receptors.
Brain Res 1985 Sep 30
PMID:Quantitative localization of [3H]TCP binding in rat brain by light microscopy autoradiography. 299 34

Photoaffinity labeling of rat brain phencyclidine (PCP) receptors with [3H] azido phencyclidine ([3H]AZ-PCP) reveals the existence of five polypeptides which are specifically labeled by the affinity probe (Mr's 90,000, 62,000, 49,000, 40,000 and 33,000). These labeled components are unevenly distributed in rat brain. In the frontal cortex, thalamus and olfactory bulb, the major bands labeled are the Mr's 90 K and 62 K polypeptides; in the cerebellum most of the labeling is in the 90 K and 33 K bands; and in the hippocampus all but the Mr 40 K band are heavily labeled. Together with dexoxadrol/[3H]PCP competition binding data, which indicated the existence of high and low affinity dexoxadrol/PCP binding sites, these results suggest regional heterogeneity of PCP receptors. The regional distribution of the high affinity dexoxadrol binding sites correlates best with that of the Mr 90 K polypeptide.
Biochem Biophys Res Commun 1985 Sep 30
PMID:Regional heterogeneity of rat brain phencyclidine (PCP) receptors revealed by photoaffinity labeling with [3H] azido phencyclidine. 299 36

Metaphit, which acylates phencyclidine (PCP) receptors in vitro, was shown to acylate PCP receptors and antagonize the behavioral and electrophysiological effects of PCP in vivo. Metaphit (2 mumol/rat) administered i.c.v. produced PCP-like stereotyped behavior and ataxia in 10 to 20% of rats. At a lower dose, Metaphit (1 mumol/rat) antagonized the ability of PCP to induce stereotyped behavior and ataxia for 3 and 4 days, respectively. The Metaphit-induced antagonism of PCP induction of stereotyped behavior and ataxia was dose-dependent and specific as Metaphit did not antagonize induction of stereotyped behavior by amphetamine. Further evidence for a specific PCP receptor mechanism was the finding that PCP pretreatment blocked the effects of subsequent Metaphit administration. Metaphit also antagonized PCP-induction of stereotyped behavior, but not ataxia, after i.v. administration. Doses of Metaphit that produced long-term antagonism of the behavioral effects of PCP also produced a significant decrease in the maximum binding, but not Kd, of the binding of the PCP analog, [3H]-1-(2-thienyl)cyclohexyl]piperidine, in Metaphit-pretreated rats. The binding of [3H]etorphine and [3H]spiroperidol was not altered significantly by pretreating rats with Metaphit. (-)-Cyclazocine and (+)-SKF 10,047 induced stereotyped behavior and ataxia that was not antagonized by Metaphit-pretreatment. In electrophysiological experiments, Metaphit, like PCP, initially depressed the firing of caudate neurons as does PCP, but then irreversibly inhibited PCP-induced depression of caudate neurons. These results suggest that metaphit antagonized the effects of PCP by selectively acylating PCP receptors and that (-)-cyclazocine- and (+)-SKF 10,047-induced behavioral effects are not mediated primarily by PCP receptors.
J Pharmacol Exp Ther 1986 Sep
PMID:Metaphit, an acylating ligand for phencyclidine receptors: characterization of in vivo actions in the rat. 301 19

Lymphocytic interstitial pneumonia is a common complication of HIV infection in children, but uncommon in adults. It is characterized clinically by the presence of cough and dyspnea, diffuse pulmonary infiltrates on chest x-ray, restrictive pulmonary dysfunction, and hypoxemia. This constellation of findings usually erroneously suggests PCP, and a lung biopsy is necessary to establish the diagnosis. Typical microscopic findings include diffuse infiltration of the pulmonary interstitium with a mixture of lymphocytes and plasma cells; immunohistologic studies reveal that in association with HIV infection, these lymphocytes are T cells. The pathogenesis of LIP in patients with HIV infection is not known. It is believed that it represents a tissue response to EBV infection, HIV infection of the lung, or both. Although patients with LIP may respond dramatically to corticosteroid therapy, others may improve with no treatment. Unfortunately, most patients eventually succumb to other complications of HIV infection.
Clin Chest Med 1988 Sep
PMID:Lymphocytic interstitial pneumonia. 304 82

The clinical significance of pulmonary function tests (including blood gas analysis) lies in their sensitivity for detecting PCP. PCP has most consistently been found to cause abnormalities in the DLCO and the exercise arterial blood gas; both are highly sensitive for the presence of Pneumocystis infection. These tests are more sensitive for the detection of PCP than are the resting arterial blood gas and chest x-ray. Therefore, measuring these values can be especially helpful in evaluating HIV-infected individuals who have pulmonary symptoms but whose resting arterial blood gas and/or chest radiograph are normal. The advantage of performing the exercise test over measuring the DLCO is that the exercise test is simple. It can be done without pulmonary function equipment and without a technologist. Furthermore, since many AIDS patients with non-PCP pulmonary disorders maintain "normal" exercise tests despite abnormal DLCO, it can be useful in evaluating patients for PCP who have known underlying lung disease with progressive symptoms. Measurement of lung volumes and spirometry lacks both sensitivity and specificity for detecting pulmonary disease in general and PCP in particular. Spirometry is helpful in detecting airways obstruction, which is not an uncommon finding in AIDS patients. The etiology, clinical significance, and treatment of obstructive ventilatory defects in the AIDS population remains unclear.
Clin Chest Med 1988 Sep
PMID:Pulmonary function tests. 304 83

A broad spectrum of lung disease occurs in association with HIV infection. Included are both infectious and neoplastic processes and idiopathic disorders. To insure prompt, accurate, and efficient diagnosis, a logical, staged sequence of tests should be applied. Chest films and, in some instances, pulmonary function tests and gallium-67 citrate lung scans serve to provide objective indications of lung disease. Each of these tests is sensitive but nonspecific. Specific infecting organisms, particularly P. carinii, can be identified by examining sputum induced by inhalation of 3 per cent saline. Bronchoscopic procedures, including BAL and TBB, are highly sensitive and should be performed in patients having nondiagnostic sputum examinations. Tests involving antigen and antibody detection are of little use in the evaluation of individual patients. Detection of recurrent episodes of PCP is difficult because abnormalities in the usual screening tests may be residual from previous episodes. Finding P. carinii in sputum or bronchoscopic specimens soon (within 2 to 3 months) after a confirmed episode of PCP likely represents residual organisms rather than recrudescence of the infection. Empiric diagnosis of P. carinii should be employed only in limited circumstances when specific diagnostic studies are not available, are contraindicated, or are refused.
Clin Chest Med 1988 Sep
PMID:Diagnosis of pulmonary diseases. 304 85


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