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

Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected intracerebroventricularly in the mouse produces two independent behavioral effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia in the acetic acid-induced writhing test and (2) motor dysfunction characterized by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan and ketamine. The specific involvement of the PCP receptor in the motor effects of Dyn Ia is supported by the direct competitive interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.
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PMID:Selective involvement of kappa opioid and phencyclidine receptors in the analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro. 135 18

[3H]Bremazocine (5 nM), in the presence of excess unlabelled mu and delta opioid ligands labelled two anatomically distinct populations of binding sites in the bovine adrenal medulla; a high density over the peripheral adrenaline-containing region of the medulla and a lower density over the central noradrenaline-containing region. This non-mu, non-delta opioid binding was specific (diprenorphine sensitive) but did not appear to involve classical kappa (kappa 1), sigma or PCP binding sites being insensitive to high concentrations of dynorphin (1-13), 3-PPP or MK-801. A significant proportion of the binding at both locations was however sensitive to competition by U50,488H or metorphamide. These data provide further evidence to support the existence of multiple opioid binding sites in the bovine adrenal medulla.
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PMID:Localisation and pharmacological characterisation of [3H]bremazocine binding in the bovine adrenal medulla. 165 8

Dynorphin and catecholamine were measured in ischemic rat produced by four-vessel (2 vertebral arteries and 2 common carotid arteries) occlusion for 10 min. The results showed that: (1) The contents of dynorphine (pg/mg tissue) in cerebral cortex were 5.5 +/- 0.6 (n = 7) in normal rats and decreased to 4.9 +/- 0.5 (n = 9, P less than 0.05) in cerebral ischemic rats; with immediate ip phencyclidine (1-(1-phenylcyclophexyl)piperidine, PCP, 1 mg.kg-1), the contents of dynorphin were increased to 5.3 +/- 0.4 (n = 5, P less than 0.05 vs the ischemic rats). (2) The contents of DOPAC (pg/mg tissue) in cerebral cortex were 38 +/- 6 (n = 7) and increased to 120 +/- 60 (n = 5, P less than 0.05) in 10 min cerebral ischemic rats; with immediately ip PCP (1 mg.kg-1), the contents of DOPAC were decreased to 26 +/- 13 (n = 7, P less than 0.05 vs the ischemic rats). (3) The release of DA (pg/mg tissue) in cortical slices in vitro, in high K+ solution were 24 +/- 3 (n = 5) and significantly increased to 57 +/- 15 (n = 5, P less than 0.05) in ischemic rat brain slices; with immediate ip PCP (1 mg.kg-1), the contents of DA were decreased to 38 +/- 10 (n = 5, P less than 0.05 vs the ischemic rats). These results suggest PCP play an antagonistic role in cerebral ischemic damage of rats.
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PMID:[Antagonistic effect of phencyclidine on cerebral ischemic damage of rats]. 172 69

Scratching induced by intrathecal (IT) administration of kainic acid (0.5 nmol) to rats was inhibited by IT pretreatment with the selective mu agonists levorphanol (30 and 90 nmol), [D-Ala2,N-Met-Phe4,Gly5-ol]-enkephalin (DAGO, 0.4 and 1.1 nmol), or morphine (90 nmol), the mixed mu-delta agonist [D-Ala2,D-Leu5]-enkephalinamide (DADLE, 10 and 30 nmol), or the sigma/phenycyclidine (PCP) agonists dextrorphan (90 nmol) or (+)-N-allyl-N-normetazocine ([+]-NAM, 90 nmol). The kappa agonists dynorphin (1.1 nmol) and ethylketocyclazocine (EKC, 90 nmol) had no significant effect, nor did the selective delta agonist [D-Pen2,D-Pen5]-enkephalinamide (DPDPE, 90 nmol). The nonopioids (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ([+]-3-PPP, 90 nmol) and PCP (90 nmol), selective for sigma and PCP sites, respectively, both antagonized kainic-induced scratching. Levorphanol- and DADLE-induced attenuation of scratching was partially antagonized by naltrexone. These findings suggest that opioid inhibition of kainic acid-induced scratching is mediated by classical mu receptors as well as sigma and PCP sites.
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PMID:Opioid inhibition of kainic acid-induced scratching: mediation by mu and sigma but not delta and kappa receptors. 215 73

The potent opiate radioligands [3H]etorphine, [3H]ethylketocyclazocine (EKC), and [3H]naloxone, bound specifically and saturably to a single class of membrane-binding sites in rat neurointermediate lobe (NIL), with Kd values of 3.7, 24, and 51 nM, respectively. In the hypothalamus (Ht), [3H]etorphine bound to specific and saturable sites with a Kd of 2.9 nM. Binding-inhibition studies with [3H]etorphine and unlabeled etorphine-HCl as well as [3H]EKC and unlabeled EKC, revealed high and low affinity binding sites in rat Ht and NIL as well as in the neural lobe of the bovine pituitary gland. [3H]naloxone also bound specifically to two classes of sites in Ht membranes, but to only a single class of low affinity sites in NIL membranes. Specific binding represented 80-90% of total [3H]etorphine binding, about 75% of total [3H]EKC binding, and 45-55% of total [3H]naloxone binding at 22 C in NIL and Ht, respectively. Relative binding potencies derived from Ki values for binding-inhibition studies of [3H]etorphine with opioid peptides and opiates were: NIL, etorphine-HCl greater than dynorphin A greater than naloxone-HCl greater than dynorphin-(1-9) greater than beta-endorphin much greater than alpha-neoendorphin approximately (Leu5)enkephalin approximately DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol); Ht, etorphine HCl greater than naloxone-HCl greater than beta-endorphin greater than dynorphin A much greater than DAGO greater than morphiceptin much greater than (Leu5)enkephalin. Specific [3H]etorphine binding was also demonstrable after preincubation of NIL membranes with DAGO and (Leu5)enkephalin and after preincubation of Ht membranes with morphiceptin and (Leu5)enkephalin; such binding could be displaced by nonradioactive dynorphin A. In addition, [3H]etorphine binding to bovine neural lobe was displaceable by naloxone-HCl, with an ED50 of 43 nM. Specific ligands for sigma-opiate receptors, such as (+)SKF 10,047 (N-allylnorcyclazocine), phencyclidine (PCP), and (-)cyclazocine, displaced specifically bound [3H]etorphine and [3H]EKC from NIL membranes only at high (micromolar) concentrations. However, specific [3H]PCP sites were of higher affinity in NIL and Ht membranes, with similar Kd values of 102 and 190 nM respectively, and different concentrations (0.15 and 1.32 pmol/mg protein, respectively). These data have revealed several differences in the opiate-binding properties of rat Ht and NIL membranes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. 303 71

The binding of [3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a KD of 23.5 +/- 7.4 nM and a low affinity site with a KD of 7.6 +/- 1.8 microM. The binding of [3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo(S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly (Ki greater than 1 microM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated (r = 0.714, P less than 0.01) with their potency to produce catalepsy in pigeons.
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PMID:Phencyclidine receptors in rat brain cortex. 609 51

The binding characteristics of [3H]Dynorphin A-(1-13) ([3H]Dyn A-(1-13) were examined in membrane preparations of rat heart. Saturation binding studies with increasing concentrations between 2.5 and 500 nM indicated that [3H]Dyn A-(1-13) binds to a single population of sites with a Kd of 285 nM and a Bmax of 215 pmol/mg protein. [3H]Dyn A-(1-13) binding is sensitive to trypsin treatment and it is inhibited by Zn2+ and Mg2+ with IC50 values of 159 and 310 microM, respectively. Dyn A and related peptides competes with the binding of [3H]Dyn A-(1-13) with the following order of potency: Dyn A-(1-13) > Dyn A > Dyn B > alpha-neo-endorphin > Dyn A-(1-8). The non-opioid peptides Dyn A-(2-13), Dyn A-(3-13) and Dyn A-(5-13) are as potent (Ki of 0.35, 0.44 and 0.59 microM, respectively) as Dyn A-(1-13) (Ki of 0.36 microM) in inhibiting [3H]Dyn A-(1-13) binding while Leu-enkephalin (Leu-Enk) exhibits no inhibitory effect at 100 microM. Selective ligands for kappa (kappa: U-50,488H, U-69,593), mu (mu: [D-Ala2, MePhe4, Glyol5]Enk) and delta (delta: [D-Ser2, Thr6]Leu-Enk) opioid receptors as well as for phencyclidine (PCP: MK-801, TCP) and sigma (sigma: (+)-SKF-10047, DTG, 3(+)-PPP) receptors show little or no inhibition of [3H]Dyn A-(1-13) binding at 100 microM. These results indicate that the heart contains a low affinity high capacity binding site for Dyn A and related peptides, distinct from opioid, PCP and sigma receptors.
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PMID:Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart. 790 2

This study examined the effects of subsequent, subchronic, treatment with choline uptake enhancer MKC-231 on the behavioral and cellular deficits induced by repeated PCP exposure in rats. Prior subchronic PCP exposure resulted in increased locomotion following an acute PCP or cocaine challenge, but resulted in decreased locomotor activity in response to a carbachol-challenge. MKC-231 significantly antagonized the alterations in the locomotor responses to cocaine and carbachol, but not to PCP. In the novel object recognition test, repeated PCP exposure caused cognitive deficits in rats, and the PCP-induced cognitive deficits were antagonized by MKC-231. In contrast, no effects of PCP exposure were shown in the repeated passive avoidance test. Furthermore, repeated PCP exposure decreased a number of choline acetyltransferase (ChAT)-positive cells in the medial septum and increased dynorphin A expression in the ventral striatum. Moreover, MKC-231 significantly antagonized the changes in septal ChAT-positive cells, but not the changes in ventrostriatal dynorphin A expression. These results suggest that MKC-231 could be a therapeutic drug for the treatment of schizophrenia.
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PMID:Subsequent exposure to the choline uptake enhancer MKC-231 antagonizes phencyclidine-induced behavioral deficits and reduction in septal cholinergic neurons in rats. 1746 60