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)

Using Northern blotting with a human genomic DNA probe for the pro-opiomelanocortin (POMC) gene, we have shown specific mRNA in normal human peripheral mononuclear cells (PBMC); the presence of specific mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We then demonstrated that PBMC translate the message into protein. Thus, using a radioimmunoassay with an antibody for ACTH, a median of 29 pg of ACTH-like immunoreactivity (ACTH-LIR) was found in 10(7) PBMC. ACTH-LIR was also detected in seven different cell lines derived from patients with lymphoid and myeloid malignancies, two of them JM and U937 showing the highest values 135 and 108 pg/10(7) cells, respectively. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH with molecular weights of the order of 31,000 POMC, 22,000 ACTH, and 4,500 ACTH, in addition to high-molecular-weight material (greater than 43,000). We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator in a similar way to lymphokines and/or may signal the adrenal gland to secrete glucocorticoids.
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PMID:Expression of pro-opiomelanocortin gene and quantification of adrenocorticotropic hormone-like immunoreactivity in human normal peripheral mononuclear cells and lymphoid and myeloid malignancies. 253 7

We examined the effect of 20 micrograms recombinant gamma-interferon (rec-gamma-IFN) upon corticotropin (ACTH) and cortisol secretion in 10 healthy male controls. We observed that rec-gamma-IFN enhances cortisol secretion with maxima around 3 hours after injection of the test dose. This effect was suppressible by a single dose of 1.5 mg dexamethasone and was not associated with increased ACTH secretion. Rec-gamma-IFN also failed to enhance ACTH secretion from a pituitary cell culture. From these data we conclude that rec-gamma-IFN acts on lymphoid cells which in turn release a yet unidentified substance that directly activates the adrenocortex in a feedback controlled manner.
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PMID:Acute adrenocortical stimulation by recombinant gamma interferon in human controls. 282 52

Infection of murine splenocytes with Newcastle disease virus results in expression of the proopiomelanocortin gene as determined by dot and northern blot analysis of total cellular and poly(A)+ cytoplasmic RNA. These data provide the first evidence that the precursor protein for adrenocorticotropin and beta-endorphin can be synthesized by lymphoid cells.
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PMID:Newcastle disease virus-infected splenocytes express the proopiomelanocortin gene. 287 61

Body, thymus, and spleen weights, and cellular makeup of lymphoid tissues of rat were not affected to a great extent by intraperitoneal injections of met-enkephalin, leu-enkephalin, or naloxone. However, enkephalins induced a diminution of peripheral blood leukocytes and lymphocytes. In addition, met-enkephalin depleted the population of T4 helper/inducer lymphocytes. On the other hand, there was an increase of blood leukocytes and lymphocytes in naloxone-treated animals. Arthus and delayed skin hypersensitivity reactions to bovine serum albumin and old tuberculin were sharply reduced in enkephalin-treated rats. Rejection of allogenic thyroid graft implanted under the renal capsule was considerably delayed by repeated injections of enkephalins. Mesenteric mast cell degranulation in rats sensitized to ovalbumin and injected with a shocking dose of antigen was less pronounced after treatment with enkephalins. These results show that enkephalins, in dosage levels of 5 mg/kg b.w., exert a suppressive influence on cell-mediated immune reactions. Other experiments from our laboratory, reported in a companion paper in this volume, suggest that much lower doses may have opposite (immunoenhancing) effects.
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PMID:Enkephalins and immunity. II: In vivo modulation of cell-mediated immunity. 349 23

Infection of hypophysectomized mice with Newcastle disease virus caused a time-dependent increase in corticosterone and interferon production. Prior treatment with dexamethasone completely inhibited the virus-induced elevation in corticosterone concentration, but did not significantly alter the interferon response. Lymphocytes appear to be the most likely source of an adrenocorticotropin-like substance that is responsible for the increased corticosterone, since spleen cells from the virus-infected, but not from control or dexamethasone-treated, hypophysectomized mice showed positive immunofluorescence with antibody to adrenocorticotropin-(1-13 amide). Thus the adrenocorticotropin-like material and interferon appear to be coordinately induced the differentially controlled products of different genes. These findings strongly suggest the existence of a lymphoid-adrenal axis.
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PMID:Virus-induced corticosterone in hypophysectomized mice: a possible lymphoid adrenal axis. 618 48

This report describes a 31-year-old woman with evidences of selective adrenocorticotropic hormone deficiency associated with a remarkable pituitary lesion, lymphoid hypophysitis. Clinical manifestations of secondary hypocortisolism, which first appeared during the immediate postpartum period following normal pregnancy, included progressive weakness and mental aberrations, fasting hypoglycemia, transient hypercalcemia, and striking ECG changes. Sudden death resulted from cardiorespiratory collapse. Microscopic examination of the anterior pituitary disclosed focal fibrosis and extensive lymphocytic infiltrations with a marked reduction of basophils; immunostaining techniques demonstrated a selective loss of corticotropin-secreting cells. The histopathology of the pituitary and its association in this case with lymphoid thyroiditis suggest that selective damage to corticotrophs was due to an autoimmune process.
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PMID:Lymphoid hypophysitis with selective adrenocorticotropic hormone deficiency. 625 May 7

The opioidergic innervation of the mammalian spleen and possible species differences were investigated. Light-microscopic immunohistochemistry revealed that splenic nerves of bovine and porcine spleen, but not of rat, mouse, hamster and guinea-pig spleen contained proenkephalin-derived opioidergic innervation. Immunoreactivity to both prodynorphin and pro-opiomelanocortin was absent from splenic nerves. In bovine and porcine spleen, fibers immunoreactive for met-enkephalin, met-enkephalin-Arg-Phe, met-enkephalin-Arg-Gly-Leu, leu-enkephalin and peptide F formed perivascular plexus, traveled in trabecular connective tissue, and extended into the capsule. Spatial relationships with immune cells were apparent in the white and red pulp, excluding lymphoid follicles. Colocalization of enkephalin immunoreactivity with immunoreactivities for tyrosin hydroxylase, dopamin-beta-hydroxylase, and neuropeptide Y, but not for substance P or calcitonin gene-related peptide were found. Our results provide evidence that opioid expression in splenic innervation is strongly species-dependent and exclusively proenkephalin-derived. Colocalization with marker enzymes of noradrenergic neurons indicates a mainly postganglionic sympathetic origin of proenkephalinergic splenic innervation. Opioidergic perivascular nerves probably control the splenic blood flow. A close interrelationship of opioidergic fibers with immune cells provides the anatomical basis for direct effects of neurally released opioids on splenic immune functions.
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PMID:Pro-enkephalin opioid peptides are abundant in porcine and bovine splenic nerves, but absent from nerves of rat, mouse, hamster, and guinea-pig spleen. 762 19

Studies on neuroendocrine hormone receptor have been hampered by low numbers and concentrations of receptors found within and outside the neuroendocrine system. The complementary peptide approach is particularly useful for dealing with this problem and has been used to characterize lymphoid receptors for arginine vasopressin (AVP), corticotropin (ACTH), substance P, and opioid peptides. A nonapeptide derived by reading of the complementary DNA strand of the bovine AVP gene in the 3' to 5' direction specifically blocks the AVP helper signal for interferon-gamma production by mouse T lymphocytes. Antibodies to 3'-5' AVP-binding peptide bound to cells, and the binding was inhibited by excess AVP. Thus, binding of anti-3'-5'AVP-binding peptide antibodies to the AVP receptor was specific. The complementary peptide approach has also been used to produce antibodies specific for the ACTH receptor complex. Complementary peptides to ACTH derived by reading in either the 5' to 3' or 3' to 5' direction were able to bind to ACTH. Monospecific antibodies to the ACTH (1-24) complementary peptide caused an ACTH-like steroidogenic response of cultured mouse adrenal cells, presumably by binding to the ACTH receptor, and binding was specifically inhibited by ACTH. The ACTH receptor complex from solubilized adrenal cells was shown to consist of four subunits with M(r) 83,000, 64,000, 52,000, and 22,000. The 83,000 and 52,000 M(r) subunits are disulfide linked and noncovalently associated with the other subunits, with binding of labeled ACTH localized to the 83,000 M(r) subunit. Similarly, a complementary peptide was shown to bind directly to substance P in a saturable and dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complementary peptides as probes to explore neuropeptide receptors on lymphocytes. 787 40

GVHD in animal models induces severe thymic atrophy as a result of prolonged secretion of high concentrations of adrenal glucocorticoids. In this study we investigated the mechanism responsible for the persistent stimulation of the adrenal glands to secrete glucocorticoids in mice undergoing GVHD. GVHD was induced across the major and multiple minor histocompatibility antigen difference in unirradiated C57Bl/6 x AF1 hybrid mice by the intravenous injection of A strain parental lymphoid cells. Our results showed plasma corticosterone (CS) levels were elevated in association with high concentrations of corticotropin (ACTH) in both the GVHD and control syngeneic (SYN) groups on day 9. By days 16 and 24, plasma CS and ACTH in the SYN mice returned to basal levels. In contrast, plasma CS levels remained elevated in the GVHD animals on days 16 and 24 despite decreasing concentrations of plasma ACTH. Reverse transcription-polymerase chain reaction (RT-PCR) showed several-fold increase in POMC mRNA in the adrenal glands of GVHD mice compared with SYN animals. In addition, high mRNA levels for murine prohormone convertase 1, the enzyme that cleaves POMC into ACTH, were also detected in GVHD adrenals. Histological analysis of GVHD adrenals failed to show any sign of adrenalitis, and RT-PCR of GVHD adrenals also failed to detect mRNA for interferon-gamma (IFN-gamma), a cytokine expressed by activated T and natural killer (NK) cells. However, mRNA for IL-12, a cytokine produced by activated macrophages, was increased in GVHD adrenals, suggesting that resident adrenal macrophages were activated during GVHD. Our findings suggest that persistent elevated levels of plasma glucocorticoids during GVHD could be mediated by intra-adrenal ACTH produced by resident adrenal macrophages activated as a consequence of GVHD.
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PMID:Increased expression of proopiomelanocortin (POMC) mRNA in adrenal glands of mice undergoing graft-versus-host disease (GVHD): association with persistent elevated plasma corticosterone levels. 853 78

Adrenocorticotropic hormone (ACTH) increases cAMP and cGMP concentrations in both adrenal and lymphoid cells, and requires extracellular Ca to have biological activity. The requirement for Ca has been difficult to characterize in terms of the channel identity and whether the committing step for steroidogenesis in the adrenal cells requires Ca. In lymphocytes, ACTH has a biphasic effect on functions such as proliferation and immunoglobin secretion. Current information is consistent with suppressive effects of high ACTH concentrations being mediated by cAMP. Stimulatory effects of ACTH concentrations are hypothesized to be mediated by Ca uptake. This review will discuss the localization of Ca signals to discrete domains within cells and the receptor- and tissue-specificity of their subcellular distribution. Considering the diversity of possible mechanisms, a hypothesis for the role of ACTH-stimulated Ca uptake during mitogen activation of T-cell lymphocytes will be presented.
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PMID:Calcium uptake by ACTH-stimulated lymphocytes: what is the physiological significance? 874 71


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