Disease relevance of p-chlorophenylalanine

• Rats injected with p-chlorophenylalanine intraventricularly began overeating after 3 days and continued to display marked hyperphagia, primarily in the daytime, accompanied by increased body weight for 1 to 2 weeks [1].
• Reserpine, p-chlorophenylalanine, or fluoxetine treatment reduces the content of serotonin in the ganglion, suggesting that the SIF cell system has properties similar to those of serotonergic neurons of the brain [2].
• p-Chlorphenylalanine effect on phenylalanine hydroxylase in hepatoma cells in culture [3].
• Whereas depletion of serotonin with p-chlorophenylalanine (PCPA) blocked the increase in hypothalamic levels of AVP and OT mRNA following osmotic stimuli in rats (2% saline drinking or dehydration), the increase in mRNA size was similar in PCPA and control animals [4].
• BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain development in a rat model in which maternal phenylketonuria (PKU) is induced by the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p-chlorophenylalanine, and L-phenylalanine in the diet [5].

Psychiatry related information on p-chlorophenylalanine

• Sleep was recorded in the rat after combined treatment with p-chlorophenylalanine (PCPA; 300 mg/kg) and 24-h sleep deprivation (SD) and then compared with sleep recorded after either treatment alone [6].
• All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established [7].
• L-5-Hydroxytryptophan microinjection (1-4 micrograms/0.5 microliters) in the anterior hypothalamus 72 h after para-chlorophenylalanine administration, restored both slow wave sleep and paradoxical sleep with variable latencies for each state of sleep [8].
• The failure of p-chlorophenylalanine to affect voluntary alcohol consumption in rats [9].
• Pretreatment with p-chlorophenylalanine (pCPA) abolished the stereotyped behaviors [10].

High impact information on p-chlorophenylalanine

• Studies in which lesions were produced with 5,7-dihydroxytryptamine and other studies in which the 5-hydroxytryptamine content was decreased with p-chlorophenylalanine indicate that some of the imipramine binding sites are on serotonin axon terminals and others are on nonserotonergic synapses [11].
• Food intake in the colitic group was assessed after depletion of brain 5-HT by p-chlorophenylalanine (PCPA) [12].
• With or without postnatal p-chlorophenylalanine treatment, 5-HTT(-/-) mice exhibited lower resting (unstimulated) lCMR(glc) than did 5-HTT(+/+) controls in the whisker-to-barrel cortex pathway and throughout the brain [13].
• Lowering brain 5-HT levels by administration of the selective tryptophan hydroxylase inhibitor p-chlorophenylalanine on postnatal days 0 and 1 restored the metabolic responses to functional activation in the whisker-to-barrel cortex pathway in adult 5-HTT(-/-) mice [13].
• Within the N-terminal sequence of 28 or 29 amino acids of hGHRH, all the analogs contained D-Arg2, Phe(4-Cl)6 (para-chlorophenylalanine), Abu15 (alpha-aminobutyric acid), and Nle27 and most of them had Agm29 (agmatine) substituents [14].

Chemical compound and disease context of p-chlorophenylalanine

• Effects of p-chlorophenylalanine and alpha-methylphenylalanine on amino acid uptake and protein synthesis in mouse neuroblastoma cells [15].
• Moreover, the reduced PGE1 bradycardia induced by p-chlorophenylalanine treatment was readily reversed by the replacement of the depleted brain serotonin with 5-hydroxytryptophan in combination with a peripheral decarboxylase inhibitor Ro4-4602 [16].
• 4 The hypothermia induced by R(-) and S(+)-DOM was antagonized by methysergide but not by p-chlorophenylalanine (PCPA) or pimozide [17].
• However, the catalepsy was not significantly antagonized by p-chlorphenylalanine (300 mg/kg X 3 days, IP) or methysergide (5, 10 mg/kg, IP), antiserotonergic drugs, and was not potentiated by the GABAergic drugs, aminooxyacetic acid (25 mg/kg, IP) or muscimol (1 mg/kg, IP) [18].
• Pretreatment with D, L-p-chlorophenylalanine methylester hydrochloride (200-400 mg/kg) significantly attenuated the mortality of the mice with pancreatitis [19].

Biological context of p-chlorophenylalanine

• The effects of beta-endorphin on the arterial blood pressure were greatly reduced in animals pretreated with p-chlorophenylalanine, a specific depletor of serotonin [20].
• In vivo tyrosine hydroxylation in rat retina: effect of aspartame ingestion in rats pretreated with p-chlorophenylalanine [21].
• The agents p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) deplete brain serotonin (5-HT) levels by two different mechanisms; PCPA inhibits the enzyme tryptophan hydroxylase, whereas PCA has a neurotoxic action on certain 5-HT neurons [22].
• 5. Depleting the rabbit's brain of 5-HT by pretreatment with p-chlorophenylalanine (PCPA) fails to affect its body temperature at thermoneutral temperatures but significantly impairs the ability to thermoregulate against a cold stress [23].
• After a single intraperitoneal injection of the irreversible tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA; 300 mg/kg), there was a rapid down-regulation of serotonin (5-HT) transporter mRNA levels in cell bodies [24].

Anatomical context of p-chlorophenylalanine

• Ultrastructural changes in rat optic nerve associated with hyperphenylalaninemia induced by para-chlorophenylalanine and phenylalanine [25].
• p-Chlorophenylalanine-induced alteration of somatodendritic levels of tryptophan hydroxylase within the rat mesencephalic raphe nuclei [26].
• In contrast with p-chlorophenylalanine, alpha-methylphenylalanine did not exert these direct toxic effects because the administration of alpha-methylphenylalanine in vivo did not affect brain polyribosomes and a comparable concentration of this analogue was neither growth inhibitory nor cytotoxic to neuroblastoma cells in culture [15].
• Spinal cord trauma inflicted on p-chlorophenylalanine-treated animals did not affect the brain peptide level at all [27].
• These effects were prevented by endogenous 5-HT depletion through pretreatment with the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA, 300 mg/kg, IP, x3), which did not significantly alter the firing characteristics of the midbrain DA cells when given alone [28].

Associations of p-chlorophenylalanine with other chemical compounds

• We can find no evidence that the loss of phenylalanine hydroxylase activity is due to: a direct inactivation of the hydroxylase by p-chlorophenylalanine or an inhibitor produced by p-chlorophenylalanine treatment; an effect similar to that of p-fluorophenylalanine; or leakage of enzyme from the cells during p-chlorophenylalanine treatment [3].
• The inhibition of 5-HT synthesis by p-chlorophenylalanine did not alter either of the two 5-HT1A sites, but deafferentation by p-chloroamphetamine caused a loss of the low-affinity [3H]8-OH-DPAT binding sites, indicating that these novel binding sites may be located presynaptically on 5-HT fibers and/or nerve terminals [29].
• After treatment with p-chlorophenylalanine, a significant decrease in the number of tryptophan hydroxylase-immunoreactive cells could be observed only in the rostral raphe dorsalis, particularly within its ventromedian and dorsomedian subdivisions [26].
• The influence of raphe lesions, p-chlorophenylalanine, and ketanserin on the estrogen-induced afternoon prolactin surge [30].
• The PRL-stimulating effect of metoclopramide (2-methoxy-5-chloroprocainamide) was examined in normal and adrenalectomized male rats pretreated with DL-p-chlorophenylalanine methyl ester (PCPA), an inhibitor of serotonin biosynthesis [31].

Gene context of p-chlorophenylalanine

• Pretreatment with p-chlorophenylalanine had no effect on the PRL secretory responses to DOM given at 0300 or 1200 h, but it attenuated the augmented PRL secretory response at 1700 h [32].
• Impairment of the serotonergic transmission by blockade of 5-HT synthesis using p-chlorophenylalanine, as well as attenuation of the noradrenergic transmission by NA depletion from terminals by DSP4, did not significantly change NPY mRNA expression or the mean number of NPY-immunoreactive neurons in the amygdala [33].
• The present study demonstrates that TPH is inhibited by a novel compound, p-ethynylphenylalanine (pEPA), produced by the Heck reaction of trimethylsilylacetylene with N-tertbutyloxycarbonyl-4-iodo-L-phenylalanine methyl ester. pEPA is a more potent and specific inhibitor of TPH than p-chlorophenylalanine (pCPA) [34].
• The increase in Arc expression induced by paroxetine/WAY 100635 was abolished by the 5-HT synthesis inhibitor, p-chlorophenylalanine (300 mg/kg i.p., daily for two days) [35].
• The 5-HT1A receptors mediating the corticosterone secretion appear to be postsynaptic to the 5-HT neurons, since the response to 8-OH-DPAT was not decreased but potentiated by depletion of 5-HT with p-chlorophenylalanine pretreatment of the animals [36].

Analytical, diagnostic and therapeutic context of p-chlorophenylalanine

• This enhancement of analgesia by intrathecal amitriptyline was prevented by pretreating the rats with p-chlorophenylalanine (300 mg/kg) [37].
• p-chlorophenylalanine increases tryptophan-5-hydroxylase mRNA levels in the rat dorsal raphe: a time course study using in situ hybridization [38].
• Reversibility of para-chlorophenylalanine-induced insomnia by intrahypothalamic microinjection of L-5-hydroxytryptophan [8].
• Met-enkephalin-Arg6-Phe7 in spinal cord and brain following traumatic injury to the spinal cord: influence of p-chlorophenylalanine. An experimental study in the rat using radioimmunoassay technique [39].
• Oral administration of p-chlorophenylalanine (PCPA, 50 mg/kg) to incubating turkeys for 3 consecutive days reduced nesting frequency (P less than 0.05) on the 4th day after initiation of treatment and the nesting virtually ceased by the 9th day [40].

References