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)

Exciting developments in knowledge of primary aldosteronism include description of new subtypes and elucidation of the genetic basis of one variety. Furthermore, relatively simple biochemical screening (aldosterone/renin ratio) has disclosed that primary aldosteronism is more common than previously thought, by diagnosing patients at an earlier, normokalaemic stage. The mutant gene discovered in the glucocorticoid-suppressible variety (FHI) codes for an aldosterone biosynythetic enzyme normally controlled by angiotensin II, and now controlled by corticotropin. The zona fasciculata is hyperplastic and makes aldosterone and "hybrid steroids" 18-oxocortisol and 18-hydroxycortisol in excess, in response to ACTH but not to angiotensin II. Adrenal tumours have not yet been described in this condition. Aldosterone-producing adenomas (Conn's syndrome) are also commonly composed of zona fasciculata-like cells, make "hybrid steroids" in excess and are very sensitive to ACTH but not to angiotensin II. We have described a new variety of aldosterone-producing adenoma which is responsive to angiotensin II (AII-responsive APA), consists of at least 20% zona glomerulosa-like cells, and does not make "hybrid steroids" in excess. We have also described a new familial variety of primary aldosteronism that includes tumours and is not glucocorticoid-suppressible (FHII). We propose that primary aldosteronism is a spectrum of genetic diseases expressed as either hyperplasia or neoplasia, and that morphological and genetic diversity explains biochemical and clinical behaviour.
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PMID:Primary aldosteronism: hypertension with a genetic basis. 135 75

Among 436 patients with hypertension unrelated to any renal lesion, renovascular damage, pheochromocytoma, Cushing's syndrome or hyperthyroidism, 15 patients had low plasma renin activity (PRA) and elevated plasma aldosterone concentrations in the upright position and resultant high aldosterone/PRA ratios: 8 with aldosterone-producing adenoma (APA; group 1) and 7 with idiopathic hyperaldosteronism (IHA; group 2). Thirty-nine patients had suppressed PRA in the presence of normal plasma aldosterone levels and moderately elevated aldosterone/PRA ratios (group 3). Thirty of them had elevated plasma 11-deoxycorticosterone (DOC) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) concentrations (group 3a) and 9 of them had normal levels of those mineralocorticoids (group 3b). The rest of them (382 patients) had low aldosterone/PRA ratios (group 4). Adrenal scintigraphy with dexamethasone pretreatment revealed [13I]-cholesterol accumulation not only in patients with APA (unilateral) or IHA (bilateral), but also in patients of group 3a (bilateral). In patients in groups 3a and 3b adrenal size (especially thickness), as measured by computed tomography (CT scan), was enlarged, as in patients with IHA (group 2), and was significantly greater than in patients of group 4 (p less than 0.001). Spironolactone reduced blood pressure in all tested patients of group 3a, and the removal of adrenal tumor or hyperplastic tissue normalized blood pressure in patients of groups 1, 2 and 3a. Excised adrenal glands exhibited cortical hyperplasia with or without nodular hyperplasia in patients of group 3a. Good agreement was found between the actual size of the excised tissue and the measurement obtained by CT scan. Since beta-endorphin and beta-lipotropin were depressed in patients of group 3a, it is suggested that an unknown pituitary substance stimulates the adrenal cortex to release too large amounts of DOC and 18-OH-DOC and inappropriate secretion of aldosterone.
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PMID:Inappropriate elevation of the aldosterone/plasma renin activity ratio in hypertensive patients with increases of 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone: a subtype of essential hypertension? 207 Mar 75

A membrane-bound aminopeptidase was purified from rat brain, and its activity was assayed by high-pressure liquid chromatography with Met-enkephalin as the substrate. The enzyme was extracted with 1% Triton X-100 and purified by chromatography, successively on DEAE-Sepharose CL-6B, Bio-Gel HTP, and Sephadex G-200 columns. The overall purification was about 1200-fold, with 25% yield. The purified enzyme showed one band on disc gel electrophoresis and two bands on sodium dodecyl sulfate electrophoresis with molecular weights of 62 000 and 66 000. The aminopeptidase has a pH optimum of 7.0, a Km of 0.28 mM, and a Vmax of 45 mumol (mg of protein)-1 min-1 for Met-enkephalin. It releases tyrosine from Met-enkephalin, but it does not split the byproduct. It does not hydrolyze gamma- or beta-endorphin, or dynorphin, but it does hydrolyze neutral and basic aminoacyl beta-naphthylamides. The enzyme is inhibited by the aminopeptidase inhibitors amastatin, bestatin, and bestatin-Gly. Its properties, such as its subcellular localization, substrate specificity, pH optimum, and molecular weight, distinguish it from leucine aminopeptidase, aminopeptidase A, aminopeptidase B, aminopeptidase M, and the soluble aminopeptidase for enkephalin degradation.
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PMID:Purification and characterization of an enkephalin aminopeptidase from rat brain membranes. 683 39

An aminopeptidase with specificity directed toward peptides with acidic N-terminal amino acid residues has been isolated from mouse brain cytosol. Purification by ion-exchange chromatography and gel filtration resulted in an enzyme that hydrolyzed aspartyl-phenylalanine methyl ester at a rate of 13.2 mumols/min/mg protein at pH 7.5, an increase in specific activity of 1000-fold over that of brain homogenate. Its apparent molecular weight, determined by gel filtration, is approximately 450,000. Dipeptides with N-terminal aspartyl residues are cleaved preferentially to glutamic-containing analogs, and a neutral amino acid (or histidine) is necessary in the adjacent position. For peptides of the form aspartyl-X, relative activity was 100, 81, 71, 66, 19, or 0, where X was alanine, serine, leucine, phenylalanine, histidine, or proline, respectively. Tripeptides were more rapidly hydrolyzed than dipeptides; however, activity tended to decline with increasing chain length. The acidic aminopeptidase can account for almost all of the activity of brain cytosol toward the N-terminal aspartyl residue of angiotensin II, aspartyl-phenylalanine methyl ester or aspartyl-alanine, and the N-terminal glutamyl residue of adrenocorticotropin(5-10). The enzyme was unaffected by bestatin or amastatin. It was inhibited by o-phenanthroline and EDTA. The latter effect could be reversed completely by Zn2+ and partially by Mn2+ or Mg2+; Co2+ and Fe2+ had no effect; Ca2+ was inhibitory. These properties distinguish the brain acidic aminopeptidase from aminopeptidase A isolated from human serum or pig kidney and the aspartyl aminopeptidase of dog kidney.
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PMID:An aminopeptidase from mouse brain cytosol that cleaves N-terminal acidic amino acid residues. 685 30

A good deal is now known about the neural circuitry involved in how conditioned fear can augment a simple reflex (fear-potentiated startle). This involves visual or auditory as well as shock pathways that project via the thalamus and perirhinal or insular cortex to the basolateral amygdala (BLA). The BLA projects to the central (CeA) and medial (MeA) nuclei of the amygdala, which project indirectly to a particular part of the acoustic startle pathway in the brainstem. N-methyl-D-aspartate (NMDA) receptors, as well as various intracellular cascades in the amygdala, are critical for fear learning, which is then mediated by glutamate acting in the CeA. Less predictable stimuli, such as a long-duration bright light or a fearful context, activate the BLA, which projects to the bed nucleus of the stria terminalis (BNST), which projects to the startle pathway much as the CeA does. The anxiogenic peptide corticotropin-releasing hormone increases startle by acting directly in the BNST. CeA-mediated behaviors may represent stimulus-specific fear, whereas BNST-mediated behaviors are more akin to anxiety. NMDA receptors are also involved in extinction of conditioned fear, and both extinction in rats and exposure-based psychotherapy in humans are facilitated by an NMDA-partial agonist called D-cycloserine. ((c) 2006 APA, all rights reserved).
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PMID:Neural systems involved in fear and anxiety measured with fear-potentiated startle. 1711 6

Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.
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PMID:Antinociceptive effect of intrathecal microencapsulated human pheochromocytoma cell in a rat model of bone cancer pain. 2500 69

This study focused on genetically determined versus acquired factors in shaping anxiety-related behavior by combining cross-breeding and cross-fostering approaches. Via cross-breeding of HAB (high anxiety-related behavior) female and LAB (low anxiety-related behavior) male mice, we obtained F1 hybrids with intermediate anxiety levels carrying genetic characteristics of both parental lines. Pups were raised either by their biological HAB (noncross-fostered control) or foster LAB (cross-fostered) mothers. Compared to controls, 6-week-old offspring raised by LAB mothers showed lower levels of anxiety in the elevated plus-maze and open field, but not the light-dark box, tests. No differences were found in the forced swim test reflecting active versus passive coping. The behavioral changes were associated with increased stress-induced concentrations of plasma corticosterone in cross-fostered animals. The expression of the corticotropin-releasing hormone receptor type I and glucocorticoid receptor genes did not differ in limbic and hypothalamic brain areas between cross-fostered and control mice. The data suggest that LAB-typical maternal care may partially shift behavioral and neuroendocrine characteristics of F1 crosses carrying both HAB and LAB alleles from intermediate toward reduced anxiety-related behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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PMID:Inborn vs. acquired anxiety in cross-breeding and cross-fostering HAB/LAB mice bred for extremes in anxiety-related behavior. 3068 86