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)

Antagonists of 4 distinct regulatory sites on the N-methyl-D-aspartate (NMDA) receptor were tested for their ability to attenuate NMDA-mediated acute excitotoxicity in isolated chick retina of various embryonic ages between days 11 and 19 in ovo. Acute excitotoxicity was monitored by histology and by release of endogenous gamma-aminobutyric acid (GABA) into the medium during 30 min of incubation with 50 microM NMDA. The uncompetitive PCP channel site antagonist, MK-801, the competitive antagonist, CGS 19755, and the strychnine-insensitive glycine site antagonist, 7-chlorokynurenate, completely blocked NMDA-induced cell swelling and increased GABA release at all ages tested. Potencies versus NMDA were MK-801 greater than CGS 19755 greater than 7-chlorokynurenate with IC50S of 0.02, 0.62, and 15 microM, respectively. NMDA antagonism by the polyamine site antagonist, ifenprodil, differed from other classes of antagonists in several respects. At the earlier embryonic ages tested (E12-13) ifenprodil provided differential protection; completely blocking somal and neuritic swelling in most but not all inner nuclear layer neurons and inner plexiform processes. In dose-response studies, ifenprodil attenuated the NMDA-induced increase in medium GABA at all ages tested with an Imax of 10 microM. Ifenprodil, however, showed a decreased ability to completely protect some NMDA-sensitive neurons. This was reflected both histologically and by GABA release. Maximal attenuation of NMDA evoked GABA release was 83, 80, 62 and 50% at days E12, 13, 15 and 19, respectively. Histologically, differential protection was seen at E12 and 13, in limited areas at E15, and was no longer present at E19.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Developmental differences in antagonism of NMDA toxicity by the polyamine site antagonist ifenprodil. 131 24

Either phencyclidine hydrochloride (PCP) (5, 10, or 20 mg/kg) or saline was administered by subcutaneous injection to gravid CF-1 mice during either Mid (E6-15) or Late (E12-18) gestation. A nontreated control group (UTC) was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Although postnatal challenge of PCP increased motor activity and ataxia in a dose-related manner, prenatal PCP had no effect on postnatal motor activity, ataxia or 3H-PCP binding. However, treatment period did have a significant effect on ataxia and 3H-PCP binding. In response to challenge doses of 5.0 and 7.5 mg/kg PCP, ataxia scores of the Late gestation offspring were significantly greater than the UTC offspring which in turn were significantly greater than the ataxia scores of the Mid gestation group. The results are discussed in relation to other animal and clinical reports of prenatal PCP exposure.
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PMID:Effects of prenatal phencyclidine on 3H-PCP binding and PCP-induced motor activity and ataxia. 279 92

Either phencyclidine (PCP) (5, 10, or 20 mg/kg) or saline was administered SC to pregnant CF-1 mice during either MID (E6-E15) or LATE (E12-E18) gestation. Because of the reported prolonged persistence of PCP in adult tissues we first determined its half-life in fetal brain for both treatment periods. PCP appeared rapidly in fetal tissues after maternal administration but was not detected after 8 hours. Then, other treated and control litters were fostered to untreated controls, growth determined and the ontogeny of isolation-induced aggressive behavior examined. Subteratogenic doses of PCP produced mild maternal toxicity without lethality. There was an apparent selective embryolethal effect on males but PCP did not produce an effect on postnatal growth. Prenatal PCP did not alter the ontogeny or intensity of isolation-induced aggressive behavior in male offspring. The results are discussed in relation to other prenatal studies of PCP toxicity and teratogenicity.
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PMID:Phencyclidine during pregnancy: fetal brain levels and neurobehavioral effects. 322 78

In mammals, hair follicles cover most of the body surface and exhibit precise and stereotyped orientations relative to the body axes. Follicle orientation is controlled by the planar cell polarity (PCP; or, more generally, tissue polarity) system, as determined by the follicle mis-orientation phenotypes observed in mice with PCP gene mutations. The present study uses conditional knockout alleles of the PCP genes Frizzled6 (Fz6), Vangl1, and Vangl2, together with a series of Cre drivers to interrogate the spatio-temporal domains of PCP gene action in the developing mouse epidermis required for follicle orientation. Fz6 is required starting between embryonic day (E)11.5 and E12.5. Eliminating Fz6 in either the anterior or the posterior halves of the embryo or in either the feet or the torso leads to follicle mis-orientation phenotypes that are limited to the territories associated with Fz6 loss, implying either that PCP signaling is required for communicating polarity information on a local but not a global scale, or that there are multiple independent sources of global polarity information. Eliminating Fz6 in most hair follicle cells or in the inter-follicular epidermis at E15.5 suggests that PCP signaling in developing follicles is not required to maintain their orientation. The asymmetric arrangement of Merkel cells around the base of each guard hair follicle dependents on Fz6 expression in the epidermis but not in differentiating Merkel cells. These experiments constrain current models of PCP signaling and the flow of polarity information in mammalian skin.
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PMID:The spatio-temporal domains of Frizzled6 action in planar polarity control of hair follicle orientation. 2651 67