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)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

1. A new line of cloned, differentiated rat hepatocytes (RL-PR-C) was evaluated for its usefulness as an in vitro system for studying the regulation of the insulin receptor. 2. Insulin rapidly reversibly and specifically bound to RL-PR-C hepatocytes. Binding of tracer 125I-labeled insulin, which was competitively inhibited by native insulin as well as by proinsulin and analogs of insulin and proinsulin in proportion to their biological activity, was not influenced by glucagon, corticotropin, or human growth hormone. Anti-insulin receptor serum from a patient with Acanthosis Nigricans Type B competed with 125I-labeled insulin for binding to cell surface sites. 3. Trypsinization destroyed insulin binding sites, but these were restored by incubation under growth conditions; a 75% restoration of binding sites was achieved by one cell population doubling. 4. RL-PR-C hepatocytes responded to insulin binding by an increase in glycogen synthesis from glucose. The insulin effect was maximal at 85 nM, but was detectable at lower, more physiological, concentrations. 5. Chronic exposure (for at least 3h) of hepatocytes to insulin (10(-10)--(10(-8) M) reduced by up to 60% the number of binding sites for insulin (down-regulation). Down-regulation was prevented by cycloheximide at concentration (10 micron) sufficient to inhibit markedly protein synthesis from tracer isoleucine. Recovery from down-regulation induced by native insulin at 10(-7 M or lower concentrations was complete by 18 h under growth conditions. 6. Although RL-PR-C hepatocytes spontaneously transform after about 90 population doublings, no significant differences between normal and transformed cells were observed in insulin binding characteristics and in interaction of cells with anti-insulin receptor serum. However, transformed cells exhibited a substantially reduced (maximum of 20%) down-regulation response to insulin. 7. RL-PR-C rat hepatocytes appear, for these reasons, to be a useful model system for studying the regulation of the insulin receptor.
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PMID:Hormone receptors. 7. Characteristics of insulin receptors in a new line of cloned neonatal rat hepatocytes. 56 93

The response of six mRNAs (for prepro-corticotropin-releasing hormone, prepro-enkephalin, prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, prepro-neurotensin/neuromedin N, prepro-cholecystokinin, and prepro-tyrosine hydroxylase) was measured in the hypothalamic paraventricular and supraoptic nuclei after increasing periods of osmotic stimulation caused by the replacement of regular drinking water with hypertonic saline (up to five days) or by forced dehydration (up to three days). In addition, hematocrits and concentrations of corticosterone were determined after the different periods of osmotic stimulation and correlated with the effects on the content of the various mRNAs. The temporal response of the mRNAs within the paraventricular and supraoptic nuclei to osmotic stimulation was different within the three compartments of these nuclei. First, in response to overnight osmotic stimulation, magnocellular neurosecretory neurons increased their mRNA content for two molecules (prepro-corticotropin-releasing hormone and tyrosine hydroxylase). As the stimulus was maintained over the next two to four days, these cells accumulated the mRNAs for at least three other peptides (cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine and enkephalin). Second, the response of peptide-coding mRNAs in parvicellular neurosecretory neurons of the paraventricular nucleus appeared to be slower; no changes could be measured after overnight stimulation. However, after a further two- to four-days of continued osmotic stimulation, the content of the mRNA coding for corticotropin-releasing hormone markedly decreased while that for cholecystokinin increased. No change in the content of the mRNAs coding for prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine, enkephalin, and prepro-neurotensin/neuromedin N could be seen at any time after osmotic stimulation in parvicellular neurosecretory neurons. Third, increases in the content of mRNA coding for corticotropin-releasing hormone in the parvicellular neurons that provide descending projections from the paraventricular nucleus could only be detected after longer periods of osmotic stimulation. The effect of osmotic stimulation on plasma corticosterone concentrations was quickly apparent; plasma corticosterone concentrations were significantly elevated on the first morning after the beginning of salt-loading, and demonstrated the rapid effects of osmotic stimulation on the mechanisms controlling corticosterone release. These results show that the synthetic capability of cells in all three compartments of the paraventricular and supraoptic nuclei are modified by osmotic stimulation over different time scales, thereby allowing differential modulation of the neuroendocrine, autonomic, and behavioral components of the animal's response to disturbances in fluid homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Disturbance of fluid homeostasis leads to temporally and anatomically distinct responses in neuropeptide and tyrosine hydroxylase mRNA levels in the paraventricular and supraoptic nuclei of the rat. 134 11

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
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PMID:Neurochemical effects of vagus nerve stimulation in humans. 150 37

The substrate specificity of polysome rat liver N alpha-acetyltransferase (NAT) has been examined by utilizing a series of synthetic and natural substrates that has been systematically altered with respect to N-terminal sequence and length. Families of peptides of the structure S-Y-S-G-G-L-L-L were generated by successively replacing the N-terminal serine, the penultimate tyrosine, and the antepenultimate serine with all 19 commonly occurring amino acids, which were then assessed for their reactivity with the rat liver enzyme. Only peptides with N-terminal serine, alanine, methionine, leucine, and phenylalanine were modified. Glycine, lysine, arginine, valine, isoleucine, and tryptophan in the second position are (with N-terminal serine) strongly inhibitory, and proline completely blocks modification. Third-position substitutions have less of an effect on NAT activity with glycine, aspartic acid, glutamic acid, and tryptophan being most inhibiting (with N-terminal Ser-Tyr). These observations are generally in agreement with in situ modifications although there are some significant differences particularly with respect to the amino-terminal residues. Optimal chain length was determined to be 10-11 residues with either synthetic peptides of the structure S-Y-S-(G)n-L-L-L or adrenocorticotropin (ACTH) sequences ranging from 8 to 39 residues. The ACTH peptides were generally found to be severalfold better substrates than the corresponding synthetic ones. Activity was not affected by increased chain length beyond approximately 17 residues. These data support the view that polysome-catalyzed N alpha-acetylation occurs as a cotranslational event on nascent chains of about 20-40 amino acids in length.
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PMID:Rat liver polysome N alpha-acetyltransferase: substrate specificity. 184 56

1. The plasma levels of L-tryptophan (L-TRP) and the sum of five competing amino acids (CAA) namely tyrosine, phenylalanine, valine, leucine, isoleucine, were determined in 79 depressed females categorized according to the DSM-III. 2. In these patients the authors measured several parameters known to affect the availability of the above amino acids, i.e. triidothyronine (FT3) and thyroxine (FT4), vanilylmandelic acid (VMA), noradrenaline and adrenaline in 24 hr urine, the sex hormonal and nutritional state. 3. The 1 mg dexamethasone suppression test was performed and the pre and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) levels were determined at 8 a.m. 4. L-TRP and the ratio L-TRP/CAA were significantly lower in severely depressed females (296.X3, 296.X4) as compared with minor (300.40, 309.00) and simple major depressives (296.X2). The ratio L-TRP/CAA performed well as a clinical tool separating melancholic from minor depression. 5. FT3, FT4, VMA and noradrenaline were significantly increased in the severely depressed females, but these data did not correlate with the availability of L-TRP. Neither baseline cortisol nor the sex hormonal, nor the nutritional state related to the L-TRP data. The ratio L-TRP/CAA was significantly and negatively correlated with the postdexamethasone cortisol and ACTH values.
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PMID:The decreased availability of L-tryptophan in depressed females: clinical and biological correlates. 217 60

Effects of adrenalectomy (ADX) or dexamethasone (DEX) treatment on the immunostaining of hypothalamic peptide histidine isoleucine (PHI) were examined in male rats. After colchicine treatment, PHI-containing cell bodies were observed in the suprachiasmatic nucleus (SCN) and the parvocellular division of the paraventricular nucleus (PVN). ADX increased and DEX dose-dependently decreased the number of PHI-immunopositive neurons in the PVN. The number of SCN-PHI neurons was not affected by any treatment employed in this study. These results suggest that PVN-PHI neurons are under the effects of the glucocorticoid milieu, and that the neurons may be involved in the glucocorticoid regulation of adrenocorticotropin and prolactin secretion.
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PMID:Effect of the glucocorticoid milieu on the immunostaining of peptide histidine isoleucine (PHI) in the rat hypothalamus. 230 37

The location and chemical identity of neurons interconnecting the lateral geniculate complex and the hypothalamus were analyzed in order to provide further information on the anatomical substrates for the entrainment of circadian rhythms. A particular objective of the study was to characterize the neurons projecting between the intergeniculate leaflet (IGL) of the lateral geniculate complex and the suprachiasmatic nucleus (SCN) and related anterior hypothalamic areas. The connectivity experiments employed five combinations of fluorescent tracer injection and were combined with immunohistochemical localization of either neuropeptide Y (NPY), met-enkephalin (mENK) or the vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI) group. IGL efferents. Injection of tracer into the SCN results in retrograde labeling of NPY-immunoreactive neurons in the IGL as would be expected from prior work. These neurons and their terminals also contain the C-flanking peptide of the NPY precursor molecule (CPON). In addition, there are two additional groups of neurons in the IGL that project either to the SCN or the contralateral IGL but do not exhibit NPY immunoreactivity. These include a substantial population of cells that project to the SCN and an even larger group of neurons which project to the contralateral IGL and contain mENK immunoreactivity. Hypothalamic efferents. Injection of tracer into the IGL results in retrograde labeling of scattered neurons throughout the SCN and immediately adjacent anterior hypothalamus ipsilaterally and also in labeling of a small number of neurons in the same areas on the contralateral side of the brain. In rare instances, individual SCN neurons appear to project to both IGLs. However, the retrochiasmatic area (RCA) contains the largest number of retrogradely labeled neurons following tracer injections into the IGL. These neurons are concentrated along the midsagittal plane and in the lateral RCA ipsilateral to the injected IGL. None of the labeled neurons in the SCN or adjacent anterior hypothalamus exhibit VIP or PHI immunoreactivity. These observations indicate that the anatomical relations between the geniculate complex and the anterior hypothalamus are more complex than previously shown. First, the geniculohypothalamic tract arises from two distinct groups of IGL neurons: one contains NPY/CPON immunoreactivity; the chemical content of the other is not characterized at the present time. Second, the commissural projection between the two IGLs is formed by a third group of neurons, and these cells contain mENK immunoreactivity. Finally, reciprocal projections from the hypothalamus to the IGL arise from neurons in the retrochiasmatic area, SCN, and adjacent anterior hypothalamus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Organization of lateral geniculate-hypothalamic connections in the rat. 275 28

Despite evidence that the branched-chain amino acids (BCAAs) influence brain metabolism and neurotransmitter synthesis, there is little information on the neuroendocrine effects of the BCAAs. We now report that administration of a mixture of the BCAAs 3 times daily for 12 days to Sprague-Dawley rats decreased the concentration of beta-endorphin immunoreactivity (BEI) in the neurointermediate lobe of the pituitary. In BCAA-treated rats, BEI was 21 +/- 4 compared to control levels of 57 +/- 12 (ng/microgram of protein). The BCAAs had no effect on the level of BEI in the adenohypophysis. These findings suggest that changes in availability of leucine, isoleucine, and valine mediate specific neuroendocrine responses to metabolic perturbations in the rat.
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PMID:Effects of branched-chain amino acids on beta-endorphin in the pituitary of the rat. 293 26

Solitary mastocytoma (mast cell naevus) of the skin represents a relatively rare dermal tumour. Its occurrence on the lower eyelid is exceptional. We report the case of a 4 month old male infant who exhibited a firm, yellowish nodule (1 cm in maximum diameter) on the lower lid of the right eye from birth. Histologically, the tumour consisted of strongly metachromatic tissue mast cells (TMC) infiltrating the whole dermis, the adjacent subcutaneous tissue and the lid muscle. Since comparable skin lesions in other sites were not observed, a diagnosis of solitary mastocytoma was made. Immunocytological investigations revealed strong reactivity of the TMC to antisera against vimentin, common leucocyte antigen (CLA), alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACT). A minor proportion of the TMC reacted to antisera against lysozyme and KiB3. Surprisingly, the TMC also reacted to antisera against certain regulatory peptides (RP), namely adrenocorticotropic hormone (ACTH), peptide histidine isoleucine (PHI), leu-enkephalin and met-enkephalin. However, absorption controls revealed that the immunostaining for ACTH and the two enkephalins was non-specific. The immunocytological phenotype of TMC suggests a close relationship to the myeloid-monocytic lineage, but a possible relationship between TMC and the diffuse neuroendocrine system needs further investigation.
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PMID:Solitary mastocytoma of the eyelid. A case report with special reference to the immunocytology of human tissue mast cells, and a review of the literature. 312 Apr 1


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