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)

Several arylcyclohexylamines and opioid benzomorphans that bind to phencyclidine (PCP) receptors were studied for their effects on punished and unpunished responding maintained under fixed-interval schedules of food presentation. All of these drugs increased both punished and unpunished responding, although higher doses decreased responding. The order of potency for increasing punished responding was MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzoa(a,d)-cyclohepten-5,1 0-imine] greater than [1-[1-(2-thienyl)cyclohexyl]piperidine] = PCP greater than (+)-N-allylnormetazocine = (-)-N-allynormetazocine. There was a high correlation (0.95) between the relative potency of these drugs in increasing punished responding and their relative affinity for PCP receptors. Because some of these drugs also bind to sigma receptors, drugs with a high affinity for sigma receptors, such as haloperidol, BD 737 [1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(1-pyrrolidinyl) cyclohexylamine] and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, were also studied for their effects on punished and unpunished responding. These drugs produced only rate-decreasing effects. The correlation between the relative potency of drugs in increasing punished responding and their relative affinity for sigma receptors was low (-0.19). These data suggest that the PCP receptor is involved in some drug-induced increases in punished responding.
J Pharmacol Exp Ther 1991 Sep
PMID:Effects of drugs that bind to PCP and sigma receptors on punished responding. 165 32

Phencyclidine (PCP) has been found to affect neuroendocrine function by altering the release of the anterior pituitary hormones, adrenocorticotrophin, luteinizing hormone and prolactin. The purpose of this study was to examine the effect of PCP on release of the two pituitary hormones also derived from the adrenocorticotropin precursor, namely, alpha-melanocyte-stimulating hormone and beta-endorphin (beta-E), synthesized in the neurointermediate and anterior lobes of the pituitary. At behaviorally active doses, PCP administered i.c.v. increased plasma levels of immunoreactive beta-E (i beta-E) without affecting the concentration of immunoreactive alpha-melanocyte-stimulating hormone, suggesting that PCP increased the release of beta-E from only the anterior lobe of the pituitary. Dexamethasone pretreatment blocked the PCP-induced increase in i beta-E which indicated further the anterior lobe effects of PCP. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate), a selective PCP ligand, at behaviorally active doses also increased the plasma concentration of i beta-E. The dose-response curves for induction of behavior was very different from that for increasing the concentration of i beta-E in plasma. The increase in release of i beta-E was stereoselective as (+)-(1-(1-phenylcyclohexyl)-3 methylpiperidine but not (-)-(1-(1-phenylcyclohexyl)-3 methylpiperidine increased release of i beta-E. The increase in plasma levels of beta-E was not due to an interaction with opioid receptors because naloxone did not block PCP-induced release of beta-E. In vitro, PCP also significantly increased release of i beta-E from anterior lobe of the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1991 Sep
PMID:Phencyclidine increased release of beta-endorphin from anterior lobe of the pituitary. 165 42

Human polymorphonuclear neutrophils (PMN) respond to ATP with an elevation in intracellular calcium and a marked enhancement of O2-production in response to stimulation by the chemotactic peptide N'-formyl-Met-Leu-Phe (FMLP). These pertussis toxin-sensitive pathways appear to be mediated by a nucleotide receptor(s) on the surface of human PMN. In the current study, we have examined the binding to intact human PMN of the ATP analog, adenosine 5'-O-(3-thio[35S] triphosphate) [( 35S]ATP gamma S). On the basis of Scatchard analysis, the binding of [35S]ATP gamma S involves at least two sites, one of high and one of low affinity. In the presence of sodium thiophosphate, a compound which did not affect intracellular increases in calcium induced by ATP or N'-formyl-Met-Leu-Phe, a significant fraction of the [35S]ATP gamma S binding was eliminated. This reduction involved both high and low affinity binding of [35S]ATP gamma S and was related to a reduction in numbers of binding sites. The Kd values for the high affinity binding site were unaffected by the presence of sodium thiophosphate, although the low affinity Kd values were numerically increased by 2-fold. In the presence of thiophosphate, [35S]ATP gamma S binding was specific, saturable, and reversible, and was related to a single class of high affinity (Kd = 36 +/- 19 nM) binding sites (184 +/- 144 sites/cell), together with a second class of low affinity (Kd = 1110 +/- 503 nM) binding sites (13,562 +/- 6,851 sites/cells). Competitive binding experiments, based on the ability of nucleotides and ATP analogs to block [35S]ATP gamma S binding to PMN, revealed a rank order of ATP gamma S greater than ATP greater than 2-MeS-ATP = 8-Bromo ATP greater than ADP = ITP greater than AMP-PCP = GTP much greater than CTP. A comparison between the ability of nucleotides to compete with [35S]ATP gamma S binding and their ability to induce a biologic response (elevation of intracellular calcium) revealed a close correlation (r2 = 0.83). These findings support the possibility of a common nucleotide PMN receptor functionally linked to a cellular response which involves increases in intracellular calcium.
Lab Invest 1991 Sep
PMID:Adenosine-5'-O-(3-thiotriphosphate) binding to human neutrophils. Evidence for a common nucleotide receptor. 165 77

The sigma receptor is a neuronal substrate that binds several psychoactive compounds. These include cocaine, some steroids, dextromethorphan, phencyclidine (PCP), and benzomorphans such as pentazocine and N-allyl-normatezocine (SKF-10047). Many newer atypical antipsychotic drugs also bind to the sigma receptor. The sigma receptor, however, is not the PCP receptor. The sigma receptor exists in the central nervous system, endocrine, immune and certain peripheral tissues. Progesterone and certain steroids have been shown to represent endogenous ligands for the sigma receptor. The sigma receptor resides likely in the nonsynaptic region of the plasma membrane. The sigma receptor exists in two forms: high-affinity and low-affinity. The solubilized sigma receptor retains all of the pharmacological characteristics of a membrane-bound receptor. A major physiological role of the sigma receptor may involve the modulation of a tonic potassium channel.
Eur J Biochem 1991 Sep 15
PMID:Sigma receptors. Putative links between nervous, endocrine and immune systems. 165 24

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.
Neurosci Lett 1991 Sep 30
PMID:Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis. 166 11

Outer membrane proteins of nontypeable (NT) Haemophilus influenzae are among the major candidates for inclusion in vaccines against these organisms. This article reports the purification of the e (P4) lipoprotein of H. influenzae and the subsequent production of antiserum directed against this protein. The anti-e polyclonal serum cross-reacted with e protein in multiple clinical NT H. influenzae isolates. Monoclonal antibody analysis of e protein showed at least one surface-exposed epitope to be conserved among NT H. influenzae strains. Anti-e serum also had bactericidal activity against multiple clinical isolates of NT H. influenzae. These results are in contrast to previous reports in the literature that purified P4 protein did not elicit biologically active antibodies. Anti-e antibodies exhibited synergistic bactericidal activity directed against NT H. influenzae when mixed with antibodies directed against another Haemophilus lipoprotein, PCP. This bactericidal synergy was observed against a variety of NT clinical isolates. We also report the cloning of the Haemophilus e lipoprotein, or hel, gene encoding the e protein and its expression and processing in Escherichia coli. The nucleotide sequence of the gene and deduced amino acid sequence of the protein are given. These results demonstrate that e protein is a viable candidate to be a component of a vaccine against NT H. influenzae.
Infect Immun 1991 Sep
PMID:The e (P4) outer membrane protein of Haemophilus influenzae: biologic activity of anti-e serum and cloning and sequencing of the structural gene. 171 22

The effect of single administrations of MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) or PCP (phencyclidine) on the induction of audiogenic seizure susceptibility by noise in immature rats was examined. Treatments with these non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists resulted in increases in noise exposure-dependent susceptibility. In neonatally drug-treated rats, seizures during adulthood were found to occur with significantly higher incidence and severity. Furthermore, drug treatments were found to lengthen what is normally a restricted developmental period within which susceptibility can be induced by noise exposure. The drugs, however, had no inherent ability to induce audiogenic seizure susceptibility if given alone. Moreover, in already-susceptible rats, MK-801 exhibited predictable anticonvulsant effects. These data suggest acute PCP or MK-801 exposures may transiently exacerbate risks inherent in certain forms of trauma. The mechanism underlying these effects is unknown although certain inferences are possible and may reveal much about epileptogenesis in this model.
Brain Res 1991 Sep 27
PMID:Sensitization to noise-mediated induction of seizure susceptibility by MK-801 and phencyclidine. 176 Jul 30

The effect of phencyclidine [1-(1-phenylcyclohexyl)piperidine, PCP] on rabbit basilar arteries was studied with an in vitro model of ring segment arteries. PCP 0.05-500 mumol.L-1 caused vasoconstriction of basilar arteries in a concentration-dependent manner. Its maximal effect (Emax) was 94 +/- 21 mg and the concentration causing half maximal effect (EC50) was 25 +/- 18 mumol.L-1. PCP 0.01-10 mumol.L-1 also concentration-dependently augmented the vasoconstriction induced by electric stimulation in rabbit basilar arteries. Its Emax was 91 +/- 18 mg and EC50 was 0.27 +/- 0.17 mumol.L-1. The effects of PCP on mean arterial blood pressure (MABP) and heart rate (HR) of rabbits were observed. PCP iv 4 mg.kg-1 reduced MABP from 14.3 +/- 0.8 to 12.2 +/- 1.0 kPa and HR from 300 +/- 0 to 278 +/- 5 bpm in 5 min. Using the technique of radionuclide imaging in rabbit brain in vivo, we studied the effect of PCP on cerebral blood flow. After iv PCP 4 mg.kg-1, the tp of radiocerebrogram was increased from 4.5 +/- 1.1 to 6.1 +/- 1.0 s, the tg of radiocerebrogram was increased from 11.7 +/- 0.6 to 18.2 +/- 3.3 s and the rate of clearance was decreased. After iv PCP 2 mg.kg-1, only tg increased from 12.6 +/- 2.1 to 15.9 +/- 0.6 s. Hence PCP increased the transit time of nondiffusible indicators (99mTc) through the cerebral circulation. These results suggest that PCP causes constriction of basilar artery and slows down the cerebral blood flow.
Zhongguo Yao Li Xue Bao 1991 Sep
PMID:[Effects of phencyclidine on rabbit basilar artery in vitro and rabbit cerebral blood flow in vivo]. 181 4

Prepulse inhibition of acoustic or tactile startle (PPI), a form of sensorimotor gating, occurs when a weak prestimulus precedes a startling stimulus and inhibits the startle response. Studies of PPI have revealed that schizophrenic patients exhibit a deficit in this form of sensorimotor gating. In rats, PPI is blocked by dopamine agonists such as apomorphine or quinpirole, effects that are antagonized by haloperidol. Phencyclidine (PCP) has been suggested as a possible model psychotogen and produces a deficit in PPI that is similar to what is observed in schizophrenic patients. Dizocilpine is an anticonvulsant drug that, like PCP, is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-induced excitations in brain and also disrupts PPI. In the present study, PPI of acoustic and tactile startle was measured in male Sprague-Dawley rats after injections of 5.0 mg/kg PCP with or without pretreatment with 0.02 or 0.1 mg/kg haloperidol, or with 0.5 mg/kg dizocilpine with or without pretreatment with 0.1 mg/kg haloperidol. The 0.1 mg/kg dose of haloperidol blocks the effects of apomorphine or quinpirole on PPI in rats. Startle was elicited by noise bursts at 105 or 120 dB or by air-puffs (tactile) and was inhibited by 75 or 85 dB prepulse stimuli presented 100 msec before the startle stimuli. The different eliciting stimuli produced different levels of startle in both control and drug-treated animals. Both NMDA antagonists significantly reduced the amount of PPI induced by the 75 dB prestimulus, independently of the level of startle responses elicited by the startle stimuli. Haloperidol did not block the disruption of PPI induced by either PCP or dizocilpine. In addition, PCP was unable to block PPI when the 85 rather than the 75 dB prepulse was used to inhibit either acoustic or tactile startle. These results confirm that putative NMDA antagonists inhibit sensorimotor gating in rats and suggest that these effects are not mediated by the activation of central dopamine systems.
Biol Psychiatry 1991 Sep 15
PMID:Failure of haloperidol to block the effects of phencyclidine and dizocilpine on prepulse inhibition of startle. 183 31

Using lead citrate as a capture reagent and adenylate-(beta, gamma-methylene) diphosphate (AMP-PCP) as a substrate, we localized adenylate cyclase activity on the non-ruffled border plasma membrane of approximately half of the osteoclasts on trabecular bone surfaces in the tibial metaphyses of chickens fed a low (0.3%)-calcium diet. The enzyme was not detectable in osteoclasts when chickens were fed a normal calcium diet. Activity was observed on the entire plasma membrane of detached osteoclasts that were situated between osteoblasts on the bone surface and blood vessels in the marrow cavity. Detection of activity on detached osteoclasts required the presence of an activator, implying lower levels in these cells than in those with ruffled borders. Staining was greater on the lateral sides of osteoblasts and osteoclasts when they were in contact with each other. Reaction specificity was indicated by the demonstration of stimulation by forskolin, guanylate-(beta, gamma-methylene) diphosphate (GMP-PCP), dimethylsulfoxide, and NaF, inhibition by alloxan and 2',5'-dideoxyadenosine, and absence of activity when sections were incubated in substrate-free medium or when GMP-PCP replaced AMP-PCP as a substrate. The finding of adenylate cyclase in osteoclast plasma membrane provides structural evidence that the adenylate cyclase-cyclic AMP system has a role in regulation of osteoclast cell function. The low-calcium diet appears to have resulted in increased amounts of adenylate cyclase in osteoclasts.
J Histochem Cytochem 1991 Sep
PMID:Ultrastructural localization of adenylate cyclase activity in chicken osteoclasts. 191 38


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