Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The single tryptophan residue in the pituitary hormone adrenocorticotropin was modified selectively by reaction with a variety of substituted o-nitrophenylsulfenyl chlorides. In addition to quantitative modification of the tryptophan residue, the reaction invariably resulted in partial oxidation of the methionine residue to the sulfoxide. The methionine sulfoxide derivative could be separated from the desired product by partition chromatography on Sephadex G-50 in the solvent system 1-butanol-pyridine-0.1% acetic acid (5:3:11). Thus, the 2,4-dinitrophenylsulfenyl, 2-nitro-4-carboxyphenylsulfenyl, and 2-nitro-4-carbamidophenylsulfenyl derivatives of adrenocorticotropin were prepared and characterized. Modifications in the isolation of adrenocorticotropin from ovine pituitaries are also described. The melanocyte stimulating activities of the native hormone and the analogues are discussed.
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PMID:Chemical modification of the tryptophan residue in adrenocorticotropin. 17 23

The developmental toxicology of 13 industrial alcohols (methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, tertiary-butanol, 1-pentanol, 1-hexanol, 2-ethyl-1-hexanol, 1-octanol, 1-nonanol, and 1-decanol), and the behavioral teratogenicity of 4 of these alcohols, were assessed in a series of experiments. The results of individual alcohols have been published previously, but the present paper summarizes the results in view of structure-activity relationships among these alcohols. The alcohols were administered by inhalation for 7 hours per day (6 hours/day for 1-decanol) on gestation days 1-19 to groups of approximately 15 pregnant Sprague-Dawley rats. For developmental toxicology evaluations, dams were sacrificed on gestation day 20. Fetuses were serially removed, weighed, sexed, and examined for external malformations. The frequency of visceral malformations and variations was determined in one-half of the fetuses, and the frequency of skeletal deviations was determined in the other half. Behavioral teratology endpoints were investigated in groups of 15 pregnant rats exposed to one of four alcohols (ethanol, 1-propanol, 1-butanol, and tertiary-butanol) and also involved groups of 18 male rats which were exposed to the same concentrations of each alcohol for 6 weeks, and then mated to untreated females. In the behavioral teratology evaluations, all litters were culled to eight pups and fostered to unexposed mothers. Offspring were tested from days 10-90 on a series of behavioral tests designed to evaluate neuromotor integrity, activity levels, learning, and memory. Additionally, brains were removed from 10 offspring per group at 21 days of age, and were dissected into cerebrum, cerebellum, brainstem, and midbrain; these samples were assayed for steady-state levels of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine (serotonin), substance P, B-endorphin, and met-enkephalin. Congenital malformations were noted for methanol, 1-propanol, isopropanol, and 1-butanol, but only at concentrations in excess of 5000 ppm. These concentrations also produced toxicity in the maternal animals; thus, there was little evidence of selective developmental toxicity among the alcohols. Although sporadic behavioral and neurochemical deviations were detected, no consistent pattern of effects was seen for any of the alcohols we tested. It should be noted that alcohols with chain lengths longer than the butyl series could not be generated as vapors at sufficiently high concentrations to produce observable toxicity in the maternal animals. This limits the generality of these findings to the possible developmental effects of these alcohols when taken through other routes of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats. 223 24

Two concentrations of 1-butanol (3000 and 6000 ppm) were administered by inhalation to separate groups of 15 pregnant Sprague-Dawley rats for 7 hr per day throughout gestation; 18 male rats were similarly exposed for 7 hr per day for 6 weeks, and mated to unexposed females. Litters were culled to 4 female and 4 male pups and fostered to untreated controls. From days 10-90, offspring were tested as follows: a) ascent on a wire mesh screen, b) rotorod, c) open field and photoelectrically-monitored activity, d) running wheel, e) avoidance conditioning, and f) operant conditioning. Additionally, brains from 10 offspring at 21 days of age were dissected into cerebrum, cerebellum, brainstem, and midbrain. Each sample was assayed for protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, serotonin, met-enkephalin, beta-endorphin, and substance P. Overall, there were few behavioral or neurochemical alterations detected in the offspring following maternal or paternal exposure to either 3000 or 6000 ppm 1-butanol. This scarcity of effects is important to risk assessment extrapolations drawn from ethanol. Based on the structural similarity of 1-butanol to ethanol and long-standing observations that toxicity to adult animals generally increases with chain length among the alcohols, significant behavioral and neurochemical deviations were predicted. The scarcity of effects from butanol needs to be accounted for in hypotheses relating toxicity to alcohol chain length and in risk assessment extrapolations from findings with ethanol.
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PMID:Behavioral teratology investigation of 1-butanol in rats. 256 63

The high affinity, sodium-dependent uptake of proline by rat brain synaptosomes was inhibited by the opioid pentapeptides, Leu-enkephalin and Met-enkephalin. The synaptosomal uptake of other putative neurotransmitter amino acids including glutamic acid, aspartic acid, gamma-aminobutyric acid, and taurine was not altered in the presence of enkephalins. The uptake of a neuroinactive amino acid, leucine, was also unaffected by enkephalins. The extent of proline uptake was half-maximal at a Leu-enkephalin concentration of 1 microM. Both the initial rate of transport and the overall capacity for proline accumulation were reduced. The effect of the enkephalins was vectorial since carrier-mediated efflux of proline was not altered in the presence of enkephalins. Morphine and the opioid peptides, dynorphin and beta-endorphin, were without effect on proline uptake. The inhibition of proline uptake by enkephalins was not diminished by prior incubation of the synaptosomal preparation with naloxone; however, the inhibition was attenuated by 1-butanol. The des-tyrosyl fragments of the enkephalins were as inhibitory as the intact pentapeptides. A modified enkephalin ([D-Ser2]Leu-enkephalin-Thr) with selective affinity for the delta subclass of enkephalin receptor was effective in inhibiting proline uptake. On the basis of the selectivity of these effects, we propose that there is a specific population of nerve endings in the cerebral cortex that contains both a proline-transport system and binding sites for Leu- and Met-enkephalin and furthermore, that these binding sites may be related to the putative delta receptor.
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PMID:Selective inhibition of synaptosomal proline uptake by leucine and methionine enkephalins. 613 50

A series of compounds related to N-butyl-N-ethyl[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amine (1, antalarmin) have been prepared and evaluated for their CRHR1 binding affinity as the initial step in the development of selective high affinity hydrophilic nonpeptide corticotropin-releasing hormone type 1 receptor (CRHR1) antagonists. Calculated log P (Clog P) values were used to evaluate the rank order of hydrophilicity for these analogues. Introducing oxygenated functionalities (delta-hydroxy or bis-beta-ethereal) into 1 gave more hydrophilic compounds, which had good affinity for the receptor. Introducing an amino group or shortening the alkyl side chain was detrimental to CRHR1 affinity. The alcohol 4-[ethyl[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amino]butan-1-ol (3), bearing a terminal hydroxyl group on an N-alkyl side-chain, showed the highest CRHR1 binding affinity among these compounds (K(i)=0.68 nM), and is one of the highest affinity CRHR1 ligands known. Compounds 3-5, and 8, which are likely to be less lipophilic than 1, have high CRHR1 affinity and may be valuable probes to further study the CRH system.
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PMID:CRHR1 Receptor binding and lipophilicity of pyrrolopyrimidines, potential nonpeptide corticotropin-releasing hormone type 1 receptor antagonists. 1173 19

The involvement of phospholipase D (PLD) in the regulation of melanogenesis was examined. Treatment of B16 mouse melanoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the activation of PLD and a decrease in melanin content. 1-Butanol, but not 2-butanol, completely blocked the TPA-induced inhibition of melanogenesis, suggesting the involvement of PLD in this event. Reverse transcription-PCR and immunoblot analyses revealed the existence of both PLD isozymes, PLD1 and PLD2, in B16 cells. When PLD1 or PLD2 was introduced into those cells by an adenoviral gene-transfer technique, both PLD1 and PLD2 were activated by TPA. When PLD1 and PLD2 were overexpressed, PLD2 potently caused a decrease in melanin content, whereas the effect of PLD1 expression on melanin content was minimal. Over-expression of PLD2 itself did not affect protein kinase C activity, as assessed by the intracellular distribution and levels of expression of each isoform expressed in B16 cells. The effects of TPA on the down-regulation of basal or alpha-melanocyte-stimulating hormone-enhanced melanogenesis were almost completely blocked by expressing a lipase activity-negative mutant, LN-PLD2, but not by LN-PLD1. Further, the PLD2-induced decrease in melanin content was accompanied by a decrease in the amount and activity of tyrosinase, a key enzyme in melanogenesis, whereas the mRNA level of tyrosinase was unchanged by the over-expression of PLD2. Moreover, treatment with proteasome inhibitors completely blocked the PLD2-induced down-regulation of melanogenesis. Taken together, the present results indicate that the TPA-induced down-regulation of melanogenesis is mediated by PLD2 but not by PLD1 through the ubiquitin proteasome-mediated degradation of tyrosinase. This suggests that PLD2 may play an important role in regulating pigmentation in vivo.
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PMID:Down-regulation of melanogenesis by phospholipase D2 through ubiquitin proteasome-mediated degradation of tyrosinase. 1506 2