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)

The effect of salmon calcitonin (SCT) on the lethality of quinolinic acid (QA), an endogenous excitatory amino acid, was investigated in relation to the excitatory amino acid receptor/ion channel complex. SCT increased the LD50 value of QA in a bell-shaped fashion, but the difference was not significant. The non competitive N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and phencyclidine (PCP) inhibited QA lethality dose-dependently. SCT potentiated the inhibitory effects of these antagonists. The competitive and glycine site antagonists 3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and 7-chlorokynurenic acid (7ClK), respectively, inhibited QA lethality in a dose-dependent fashion. SCT did not potentiate the effect of either drug. These results suggest that SCT inhibits NMDA receptors by interacting with Ca ion channel.
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PMID:Effect of salmon calcitonin on the lethality of quinolinic acid, an excitatory amino acid. 133 50

Despite these potential problems, biochemical bone markers are the single most sensitive method for monitoring acute changes in bone metabolism. For example, subcutaneous injections of recombinant human insulin-like growth factor I cause a measurable increase in both procollagen and urinary DPD in as little as 1 day. Similarly, it is possible to measure a significant decrease in bone formation as determined by decreases in serum levels of ALP, OC, and C-PCP within 12 hours after the beginning of a PTH infusion study. Additionally, an increase in DPD/cr was determined within 24 hours of the start of bed rest. These changes, seen within 24 hours, are far earlier than could be detected by any other method of monitoring bone metabolism. Thus, biochemical assays have opened a new era where changes in bone metabolism can be detected in hours to days. This acute detectability should be especially helpful to the development of new drugs and the optimization of the use of approved drugs. Accordingly, definite dose-response studies can now be done in a reasonable time. For osteoporosis therapy there are reasons to consider cyclic drug administration, such as avoiding drug resistance (PTH or calcitonin), avoiding overtreatment (bisphosphonates), or avoiding a possible mineralization defect (fluoride). By using biochemical assays, we can determine the optimum amount of "on time" and "off time" in cyclic therapy. Of the bone formation assays, ALP, OC, and PCP, we recommend for routine use the OC assay because of its high discriminant power and because it has been better characterized, in terms of clinical application, than the PCP assays and the ALP IRMA. If, however, the serum cannot be drawn at a specific time in all patients to be studied, we recommend the ALP assay because, unlike the OC assay, it shows no diurnal variation. Of the bone resorption assays, HYP, TRAP, GHYL, and PYD/DPD, we recommend the urine PYD/DPD assay (adjusted for creatinine) because it is commercially available and because, along with the urine GHYL assay, it is the most sensitive bone resorption assay. Established guidelines for the use of assays in patient care is not yet available, largely because of the large intrapatient variation seen with most assays. Once this problem is resolved, it should be possible to apply biochemical assays to routine clinical practice. For example, if the patient has a urine DPD/cr (indicating a high bone resorption rate), the patient would be selected for antiresorptive therapy, and subsequently the urine DPD/cr assay would be repeated during therapy to determine the effective dose of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical markers of bone turnover for the clinical assessment of bone metabolism. 798 80

Calcitonin gene-related peptide (CGRP) is the major product of the calcitonin gene in brain and exerts a number of actions in the central nervous system (CNS). In particular the finding that CGRP affects dopamine (DA) release and metabolism has raised the possibility that it may play a role in several neuropsychiatric disorders. Consequently, we have here studied the effects of two psychotomimetic drugs, namely, d-amphetamine (AMPH) and phencyclidine (PCP), on CGRP concentrations in brain microdialysates from freely moving rats. The animals were stereotaxically implanted with vertical concentric probes in the medial prefrontal cortex (mPFC), the ventral striatum (vSTR), or the hippocampus; and the experiments were performed 48 hr after surgery. The dialysis probes were perfused with a modified Ringer's solution at the rate of 5 microliters/min. AMPH 1.5 mg/kg, PCP 2.5 mg/kg, or NaCl 0.9% were injected s.c.; and the perfusates were collected at 60 min intervals before and after the injections and used for CGRP-like immunoreactivity (-LI) determination by radioimmunoassay (RIA). In separate experiment, KCl (100 mM), veratridine (50 microM), or tetrodotoxin (2 microM), were added to the perfusate and infused in the vSTR. Baseline levels of CGRP-LI were detected in dialysates from all three regions. Both AMPH and PCP caused a significant and sustained increase (maximum about 300%) in CGRP-LI concentrations, in particular from the mPFC and vSTR, while saline had no effect. KCl and veratridine also increased CGRP-LI in dialysates during the first posttreatment period, while tetrodotoxin induced a significant but delayed decrease in CGRP-LI levels. Finally, cervical dislocation also elevated CGRP-LI in dialysates from the mPFC and the vSTR. Our findings demonstrate that 1) CGRP-LI can be measured in vivo in microdialysates from mPFC, vSTR, and hippocampus; 2) the release in vSTR is action potential-dependent; and 3) systemic administration of AMPH or PCP results in a long-lasting release of CGRP-LI in the mPFC and vSTR, thus demonstrating a novel action of these drugs in the brain. Since other studies have shown that major antipsychotic drugs appear to reduce CGRP release in brain, our study provides, in principle, support for a role of CGRP in psychotic disorders.
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PMID:The psychotomimetic drugs D-amphetamine and phencyclidine release calcitonin gene-related peptide in the limbic forebrain of the rat. 893 70