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 potent hypotensive peptide, adrenomedullin (AdM), originally isolated from a human pheochromocytoma is present in a variety of rat and human tissues. We examined its potential effects in anterior pituitary gland, reasoning that it may be a feedback regulator of adrenocorticotropin (ACTH) secretion. Rat AdM11-50 inhibited basal ACTH secretion from dispersed, rat anterior pituitary cells in a significant, dose-related fashion (maximum inhibition at 10(-9) M). Rat AdM11-50 also inhibited, in a dose-related fashion, corticotropin releasing hormone (CRH)-stimulated ACTH secretion, but did not block the ability of CRH to stimulate cAMP accumulation in these cells. These findings suggest that in addition to peripheral actions in the vasculature and kidney, adrenomedullin may act within the anterior pituitary gland to control fluid and electrolyte homeostasis.
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PMID:A novel vasoactive peptide, adrenomedullin, inhibits pituitary adrenocorticotropin release. 772 Jun 84

The recently discovered peptide adrenomedullin (AM) alters blood pressure through effects on the resistance vessels. Moreover, AM modifies the secretion of corticotropin and aldosterone and could thereby indirectly influence blood pressure through the renin-angiotensin-aldosterone system. Although plasma AM and renin concentration have been found to directly correlate, a causal linkage between AM and renin has not been shown. The present study tested the influence of AM on renin secretion and renin gene expression by renal juxtaglomerular granular cells. Prominent expression and release of AM by vascular structures has been reported; therefore, we investigated the local expression of AM in juxtaglomerular structures. Renin release from isolated perfused rat kidneys was dose-dependently increased by AM (1 to 30 nmol/L), whereas renal perfusate flow rate increased up to 17% at a constant perfusion pressure of 100 mm Hg. In primary cultures of mouse granular cells, AM augmented renin release, renin mRNA accumulation, and cAMP production in a dose- and time-dependent manner (threshold values in the range 10 pmol/L to 1 nmol/L). By reverse transcription-polymerase chain reaction, significant expression of the AM gene was detected in microdissected rat glomeruli with afferent arterioles and in primary cultures of mesangial and granular cells. We conclude that AM is expressed in juxtaglomerular structures and that it has a direct stimulatory effect on renin secretion and renin mRNA abundance by receptors on juxtaglomerular cells, possibly through increases in cAMP. AM could act as an autocrine/paracrine stimulatory factor in the control of renin secretion and renin gene expression.
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PMID:Adrenomedullin stimulates renin release and renin mRNA in mouse juxtaglomerular granular cells. 914 80

Two potent hypotensive peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP), are encoded by the adrenomedullin gene. AM stimulates nitric oxide production by endothelial cells, whereas PAMP acts presynaptically to inhibit adrenergic nerves that innervate blood vessels. Complementary, but mechanistically unique, actions also occur in the anterior pituitary gland where both peptides inhibit adrenocorticotropin release. In the adrenal gland both AM and PAMP inhibit potassium and angiotensin II-stimulated aldosterone secretion. Natriuretic and diuretic actions of AM reflect unique actions of the peptide on renal blood flow and tubular function. In the brain AM inhibits water intake and, in a physiologically relevant manner, salt appetite. Both AM and PAMP act in the brain to elevate sympathetic tone, effects that mirror the positive inotropic action of AM in the heart. Cardioprotective actions in the brain and heart may be important counter-regulatory actions that buffer the extreme hypotensive actions of the peptides when released in sepsis. Thus the biologic actions of the proadrenomedullin-derived peptides seem well coordinated to contribute to the physiologic regulation of volume and electrolyte homeostasis.
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PMID:Adrenomedullin and the control of fluid and electrolyte homeostasis. 1009 93

Preproadrenomedullin is processed into at least two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP). Both peptides are hypotensive; however, they exert this action via differing mechanisms. In pituitary cells in culture, both basal and releasing factor-stimulated adrenocorticotropin (ACTH) secretion is inhibited by AM. Here we report that basal, but not stimulated, ACTH secretion from cultured rat pituitary cells is also inhibited by PAMP. The effect is dose-related, occurs in a physiologically relevant dose range that is similar to that of AM, and is blocked by the potassium channel blocker, glybenclamide. The failure of glybenclamide to inhibit AM's effects on ACTH secretion indicates that in pituitary, as in other tissues, these two products of the same prohormone can exert similar biologic activity, although via differing mechanisms.
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PMID:Proadrenomedullin N-terminal 20 peptide inhibits adrenocorticotropin secretion from cultured pituitary cells, possibly via activation of a potassium channel. 1022 92

The production and secretion of peptides by adrenocortical tumors have not been well studied. We therefore studied the production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1 in SW-13 human adrenocortical carcinoma cells by radioimmunoassay and Northern blot analysis. Both immunoreactive-adrenomedullin and immunoreactive-endothelin were detected in the culture medium of SW-13 cells (27.7 +/- 1.6 fmol/10 (5) cells/24 h and 11.0 +/- 0.8 fmol/10 (5) cells/24 h, respectively, mean +/- SEM, n = 6). Northern blot analysis showed the expression of adrenomedullin mRNA and endothelin-1 mRNA in SW-13 cells. On the other hand, no significant amount of calcitonin gene-related peptide, corticotropin-releasing hormone, neuropeptide Y, or urocortin was secreted by SW-13 cells. Treatment with ACTH (10(-9)-10(-7) mol/l), angiotensin II (10(-9)-10(-7) mol/l), or dexamethasone (10(-8)-10(-6) mol/l) for 24 h had no significant effects on immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium of SW-13. Treatment with tumor necrosis factor (TNF)-alpha (20 ng/ml) increased significantly both immunoreactive-adrenomedullin levels and immunoreactive-endothelin levels in the culture medium. Interferon-gamma (100 U/ml) increased the immunoreactive-endothelin levels, but not immunoreactive-adrenomedullin levels, whereas interleukin-1 (IL-1)beta (10 ng/ml) increased immunoreactive-adrenomedullin levels, but not immunoreactive-endothelin levels. These findings indicate that SW-13 human adrenocortical carcinoma cells produce and secrete two vasoactive peptides, adrenomedullin, and endothelin-1 and that the secretion of these two peptides is modulated differently by cytokines.
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PMID:Production and secretion of two vasoactive peptides, adrenomedullin and endothelin-1, by cultured human adrenocortical carcinoma cells. 1076 53

It has been demonstrated that adrenomedullin, a newly discovered peptide with structural similarity to calcitonin gene-related peptide (CGRP), is expressed in pituitary gland and affects basal and corticotropin (ACTH)-releasing factor (CRF)-stimulated ACTH release in animals, thus suggesting its potential role in regulating the hypothalamus-pituitary-adrenal axis. To evaluate whether ACTH and cortisol levels affect adrenomedullin production in humans, we studied 14 patients with Cushing's syndrome due to pituitary adenoma and 8 patients with Cushing's syndrome due to adrenal tumor, with measurement of circulating adrenomedullin by a specific radioimmunoassay (RIA). Adrenomedullin concentrations were significantly higher in patients with pituitary adenoma (37.6 +/- 17.8 pg/mL) versus controls (13.7 +/- 6.1 pg/mL) and patients with adrenal adenoma (17.8 +/- 2.2 pg/mL). After pituitary surgical treatment, plasma adrenomedullin decreased significantly. In one patient with Cushing's syndrome due to pituitary adenoma who underwent simultaneous sampling of the inferior petrosal venous sinuses, the adrenomedullin concentration was significantly higher in plasma collected from the side with the adenoma and increased after CRF administration (delta increase, 42.6%), according to ACTH levels. Our findings indicate that circulating adrenomedullin is increased in Cushing's disease, and the pituitary gland may represent the site of the elevated production of adrenomedullin in this condition.
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PMID:Circulating adrenomedullin is increased in patients with corticotropin-dependent Cushing's syndrome due to pituitary adenoma. 1087 3

In the last several decades, the concept of "endocrinology" has been greatly changed. One major change was due to the discovery of peptide hormones secreted by the organs that were not "classical" endocrine organs. For example, corticotropin-releasing hormone and many neuropeptides are secreted by the neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular endothelial cells, and leptin by the adipose tissues. Now, the brain, heart, vascular tissue and adipose tissue can be considered to be endocrine organs. Cardiovascular diseases and obesity are therefore important targets of the endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of 52 amino acids. It was originally discovered from a human pheochromocytoma, and belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is produced and secreted by various types of cells, for example, vascular endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous expression has not been observed in other neuropeptides, including neuropeptide Y and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory cytokines. In addition to vasodilator actions, this peptide has central inhibitory actions on water drinking and salt appetite, effects on the secretion of some hormones and cytokines, inotropic actions and effects on cell growth and apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as endocrine tumors, and acts as a growth stimulatory factor for the tumor cells. Adrenomedullin seems to be involved in the pathophysiology of many diseases, including ischemic heart diseases, inflammatory diseases, tumors, and even eye diseases. The adrenomedullin research implies that "the neuroendocrine system" exists in much broader types of cells than previously thought, and that the endocrine research is able to contribute to the understanding of the pathophysiology of many diseases.
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PMID:Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century. 1131 31

Adrenomedullin, a potent vasoactive peptide, is actively secreted from primary cultures of human oral and skin keratinocytes, but nothing is known of the regulation of its release. This study describes the effects of a range of substances on adrenomedullin production from cultures of oral and skin keratinocytes. We have established that keratinocytes do not store adrenomedullin but secrete it constitutively. Cytokines interleukin-1alpha and -1beta, tumor necrosis factor-alpha and -beta, and the bacterial product, lipopolysaccharide, significantly stimulate adrenomedullin secretion from oral but not skin keratinocytes. Both transforming growth factor-beta1 and interferon-gamma are potent suppressors of adrenomedullin secretion from both cell types, as are forskolin, di-butyryl cyclic adenosine monophosphate, and adrenocorticotropin. The peptides thrombin and endothelin-1 increase adrenomedullin production, particularly from skin keratinocytes. These findings indicate that there are differences in the regulation of adrenomedullin production between oral and skin keratinocytes and that oral keratinocytes are particularly responsive to the action of inflammatory cytokines. This raises the possibility that adrenomedullin may serve a different functions in oral mucosa and skin.
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PMID:Regulation of adrenomedullin secretion in cultured human skin and oral keratinocytes. 1151 15

The expression of components of the adrenomedullin (AM) system (AM and its receptors) has been detected in mammalian adrenal zona glomerulosa (ZG) cells, and evidence has been provided that AM is able to inhibit agonist-stimulated aldosterone secretion from and to enhance the proliferative activity of ZG cells. However, there has been no evidence that the endogenous AM system acts as a physiological regulator of ZG function. Hence, we investigated whether the suppression of AM gene transcription by a specific antisense oligodeoxynucleotide (ODN) is able to alter the secretion and growth of rat ZG cells cultured in vitro. ZG cell cultures were examined 0, 2, 4, 6 and 8 days after treatment with scrambled sense (S)-ODN (control cultures) and AM antisense (A)-ODN. Control cultures, as well as freshly dispersed ZG cells and ODN-untreated cultures, expressed AM as mRNA and protein. A-ODN treatment suppressed AM expression within 4 days and the suppression lasted until day 6. Confluent control cultures displayed basal and angiotensin-II (Ang-II), K(+)- and adrenocorticotropic hormone (ACTH)-stimulated aldosterone secretions similar to those of ODN-untreated cultures. A-ODN treatment magnified the aldosterone response to Ang-II and K+ at days 4 and 6 (but not at day 8), without affecting the basal or ACTH-stimulated secretion. As compared to ODN-untreated and control cultures, non-confluent A-ODN-treated ones showed a 40% elongation in the duplication time, a significant decrease in the proliferation index, and a marked rise in apoptotic index from day 4 to day 8. In conclusion, our study validates the use of A-ODN to block the endogenous AM system, showing that suppression of AM-synthesis requires at least 2 days to become appreciable and persists for at least 6 days. Moreover, it provides the first evidence that endogenous AM plays a physiological role in cultured rat ZG cells, by exerting a buffering action on their acute secretory response to Ang-II and K+ and by maintaining normal basal proliferative and apoptotic activities.
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PMID:Role of the endogenous adrenomedullin system in regulating the secretion and growth of rat adrenal cortex. 1263 Aug 16

Intermedin/Adrenomedullin-2 (IMD), a newly described peptide with structural homology to adrenomedullin (AM), is present in brain and pituitary gland and binds to the same receptors as AM and calcitonin gene-related peptide (CGRP). We hypothesized that IMD would exert actions similar to AM and CGRP and previously have demonstrated that indeed IMD, like AM and CGRP, increases sympathetic tone and inhibits feeding and drinking when administered centrally. Here, we extend those observations by demonstrating that like AM, IMD acts in brain to stimulate the secretions of prolactin (PRL) and adrenocorticotropin (ACTH) and to inhibit the secretion of growth hormone (GH) in conscious rats. In addition, in conscious rats, central administration of IMD results in increased plasma levels of oxytocin (OT) and vasopressin (AVP). The ability of IMD to activate the hypothalamo-pituitary-adrenal (HPA) axis can be blocked by intravenous pretreatment with the corticotropin releasing factor (CRF) antagonist, astressin. These results suggest that multiple members of the AM family of peptides may be involved in the cardiovascular, behavioral and neuroendocrine responses to stress.
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PMID:Stress hormone secretion is altered by central administration of intermedin/adrenomedullin-2. 1591 Jul 78


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