Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031511 (pheochromocytoma)
 14,622 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of synthetic rat adrenomedullin (rAM), a novel vasorelaxant peptide originally isolated from human pheochromocytoma, on receptor binding and cAMP generation were studied in cultured rat vascular smooth muscle cells (VSMC). A binding study using [125I]rAM revealed the presence of a single class of high-affinity (Kd 1.3 x 10(-8) M) binding sites for rAM in VSMC. The apparent Ki of rat calcitonin gene-related peptide (rCGRP) was 3 x 10(-7) M. Affinity labeling of VSMC membranes with [125I]rAM revealed two distinct labeled bands with apparent molecular weights of 120 and 70 kDa, both of which were abolished by excess unlabeled rAM or rCGRP, rAM stimulated cAMP formation with an approximate EC50 of 10(-8) M, the effect of which was additive with isoproterenol, but not with rCGRP. The rAM-induced cAMP response was unaffected by propranolol, indomethacin, or quinacrine, but inhibited by a CGRP receptor antagonist, human CGRP[8-37]. These data suggest that VSMC possesses specific AM receptors functionally coupled to adenylate cyclase with which CGRP interacts.
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PMID:Specific receptors for adrenomedullin in cultured rat vascular smooth muscle cells. 813 50

A novel hypotensive peptide was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. Since this peptide is abundant in normal adrenal medulla as well as in pheochromocytoma tissue arising from adrenal medulla, it was designated "adrenomedullin". The peptide, consisting of 52 amino acids, has one intramolecular disulfide bond and shows slight homology with calcitonin gene related peptide. It was found to elicit a potent and long lasting hypotensive effect. The peptide circulates in blood in a considerable concentration, but it was not found in brain. These data suggest that adrenomedullin is a new hormone participating in blood pressure control. Occurrence of adrenomedullin indicates the possible existence of a novel system for circulation control.
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PMID:Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. 838 82

Adrenomedullin is a novel hypotensive peptide recently discovered in human pheochromocytoma. In the present study, we measured the plasma immunoreactive adrenomedullin of healthy subjects and patients with various diseases. Immunoreactive adrenomedullin was found to circulate in blood of the healthy subjects at a considerable concentration (3.3 +/- 0.3 fmol/ml). Plasma adrenomedullin was significantly increased in the patients with congestive heart failure (5.4 +/- 0.3 fmol/ml), essential hypertension (5.3 +/- 0.4 fmol/ml) and renal disease (4.9 +/- 0.4 fmol/ml). In healthy volunteers physical exercise significantly increased the plasma adrenomedullin concentration. The increase of adrenomedullin was inversely related to systolic blood pressure. These findings indicate that adrenomedullin participates in the circulation control in both physiological and diseased conditions. Although the exact origin of circulating adrenomedullin is still unknown, it is thought to be released rapidly by acute exercise, thereby regulating the cardiovascular system by its vasodilating activity.
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PMID:Plasma adrenomedullin in various diseases and exercise-induced change in adrenomedullin in healthy subjects. 856 10

Adrenomedullin has recently been isolated from human pheochromocytoma. We designed the present study to examine the effect of adrenomedullin on the production of the vasoconstrictive and growth-promoting peptide endothelin-1 (ET-1) after stimulation with platelet-derived growth factor (PDGF) in cultured rat glomerular mesangial cells. PDGF stimulated ET-1 production in a concentration-dependent manner. Rat adrenomedullin inhibited this stimulated ET-1 production in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Rat adrenomedullin also increased the cellular level of cAMP in a concentration-dependent manner between 10(-7) and 10(-8) mol/L. Human adrenomedullin was less effective than rat adrenomedullin with respect to inhibiting ET-1 production and increasing cAMP levels. The addition of 8-bromo-cAMP (10(-3) and 10(-4) mol/L) reduced PDGF-induced ET-1 production. Furthermore, forskolin (10(-4) and 10(-5) mol/L), an activator of adenylate cyclase, reduced PDGF-induced ET-1 production. In contrast, the basal production of ET-1 was not significantly altered by rat and human adrenomedullin. These results indicate that adrenomedullin inhibits PDGF-induced ET-1 production in cultured rat mesangial cells, probably through a cAMP-dependent process.
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PMID:Interaction of adrenomedullin and platelet-derived growth factor on rat mesangial cell production of endothelin. 861 21

Human adrenomedullin (hAM), a potent vasodilatory peptide originally identified in pheochromocytoma, has been shown to be present in various human tissues and circulate in human plasma. We measured plasma concentrations of immunoreactive hAM in patients with sepsis who had been admitted to intensive care unit (ICU). Plasma hAM concentrations in 12 septic patients upon entering the ICU were extremely elevated (107 +/- 139 fmol/ml: mean +/- SD) compared to those of 16 age-matched normal subjects (7.9 +/- 3 fmol/mL). Among 10 patients with normal renal function, plasma hAM levels either decreased or increased during the hospital course; the former group survived and the latter group succumbed. Two patients with acute renal failure had markedly elevated plasma hAM levels during the early course, which declined rapidly during the recovery course. High performance liquid chromatography of plasma extracts from one patient with acute renal failure revealed a single major component of immunoreactive hAM coeluting with authentic hAM (1-52) during acute and recovery phase. Plasma hAM concentration showed positive correlations with heart rate, right atrial pressure, and serum creatinine concentration, but not with other hemodynamic variables. These data suggest that a marked increase in circulating hAM in sepsis may be caused by its decreased clearance and/or its enhanced synthesis by multiple organ dysfunction, and that increased endogenous hAM may be involved in the mechanism of cardiovascular abnormalities associated with sepsis.
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PMID:Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis. 863 49

Adrenomedullin (ADM) is a new 52 amino acid peptide originally isolated from extracts of human pheochromocytoma. ADM's biologic properties are nearly identical to those of atrial natriuretic peptides. Thus, the 4 peptide hormones originating from amino acids 1-30 [long acting natriuretic peptide], 31-67 [vessel dilator], 79-98 [kaliuretic peptide] and 99-126 [atrial natriuretic factor; ANF] of the 126 amino acid ANF prohormone as well as ADM have blood pressure lowering and diuretic properties. The present investigation was designed to determine if one or more of these 4 atrial natriuretic peptides increase adrenomedullin within the circulation of healthy humans. Infusion of 100 ng/kg body weight/minute for 60 minutes of the respective atrial peptides resulted in a 4-fold (P < 0.001) increase in the circulating concentration of adrenomedullin secondary to the ANF infusion but no increase in adrenomedullin with the long acting natriuretic peptide, vessel dilator, or kaliuretic peptide infusions. The four-fold increase of adrenomedullin in the circulation persisted throughout the infusion of ANF, but returned to pre-infusion levels within 30 minutes of stopping the ANF infusion. Infusion of 10 pg/kg body weight/minute for 60 minutes of ANF resulted in a 2 1/2-fold increase (P < 0.05) in the circulating concentration of adrenomedullin. There was a significant (P < 0.01) diuresis and blood pressure lowering effect with each of the atrial natriuretic peptides in the present investigation. This investigation suggests that 1) atrial natriuretic factor increases the release of adrenomedullin and 2) that the diuretic and blood pressure lowering effects previously attributed to atrial natriuretic factor may be partially due to adrenomedullin since both increased during the ANF infusion and both have similar biologic effects. As opposed to atrial natriuretic factor, adrenomedullin was not increased by long acting natriuretic peptide, vessel dilator, or kaliuretic peptide suggesting that their biologic effects do not involve adrenomedullin.
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PMID:Atrial natriuretic peptide increases adrenomedullin in the circulation of healthy humans. 869 35

Adrenomedullin is a fifty-two-amino acid polypeptide that was first discovered in pheochromocytoma cells, and later in the normal adrenal medullae, lungs, kidneys, and blood. In mammals, adrenomedullin has vasodepressive effects, mainly by decreasing peripheral vascular resistance. I investigated the effects of adrenomedullin in fish to see if this novel neuropeptide would have an effect in lower vertebrates, or if its actions were limited to the higher vertebrates. Bolus injections of adrenomedullin resulted in a reduction of heart rate and dorsal aortic pressure in the rainbow trout Oncorhynchus mykiss. However, adrenomedullin had no effect in the Atlantic cod, Gadus morhua. The effects of adrenomedullin in trout appear to be due to a direct action on the peripheral vasculature, as pre-treatment of celiac artery strips with tetrodoxin had no effect on the ability of adrenomedullin to relax the strip.
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PMID:Cardiovascular effects of adrenomedullin in teleost fishes. 872 51

Adrenomedullin is a potent vasodilator peptide that was isolated from pheochromocytoma. Localization of adrenomedullin-like immunoreactivity was studied by immunocytochemistry in the human hypothalamus and adrenal gland. Adrenomedullin-immunoreactive cell bodies were found in the paraventricular, supraoptic and infundibular nuclei of the hypothalamus. Both magnocellular and parvocellular cells of the paraventricular nucleus were positively immunostained. Adrenomedullin-like immunoreactivity was localized in the adrenal medulla. No positive immunostaining was observed in the vascular endothelium, vascular smooth muscle cell or adrenal cortex. The preabsorption of the antiserum with synthetic human adrenomedullin (1-52) abolished the immunostaining. These findings indicate that adrenomedullin-like immunoreactivity is localized in the paraventricular, supraoptic and infundibular nuclei as well as in the adrenal medulla, and suggest that adrenomedullin acts as a neurotransmitter, a neuromodulator or a neurohormone in the human hypothalamus.
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PMID:Immunocytochemical localization of adrenomedullin-like immunoreactivity in the human hypothalamus and the adrenal gland. 874 29

Adrenomedullin is a novel hypotensive adrenal polypeptide originally isolated from a human pheochromocytoma and is structurally related to calcitonin gene-related peptide and islet amyloid polypeptide. Using immunocytochemistry, the occurrence of adrenomedullin in the adrenal gland and gastro-entero-pancreatic region in the rat was examined and its effect on insulin secretion from isolated rat islets was determined. Adrenomedullin-like immunoreactivity occurred in noradrenaline- and adrenaline-producing cells in the adrenal gland. Gastrointestinal endocrine cells, with increased density distally, displayed adrenomedullin-like immunoreactivity; these cells constituted a subpopulation of the enterochromaffin (serotonin-containing) cells. Co-localization of adrenomedullin with somatostatin, glicentin, gastrin/cholecystokinin, peptide YY or islet amyloid polypeptide was not encountered. Adrenomedullin-immunoreactive cells were not observed in the pancreatic islets. At 1, 10 and 100 nmol/l, adrenomedullin stimulated insulin release from isolated rat islets in the presence of 3.3 mmol/l glucose (P < 0.05) and at 100 nmol/l, the peptide potentiated insulin secretion also in the presence of 8.3 mmol/l glucose (P < 0.05). These findings suggest that, besides being an adrenal hypotensive peptide, adrenomedullin may be a gut hormone with a potential insulinotropic function.
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PMID:Adrenomedullin: localization in the gastrointestinal tract and effects on insulin secretion. 879 72

Although initially described in human pheochromocytoma, adrenomedullin has been isolated in several animal and human peripheral organs, including cardiovascular tissues. In experimental models, adrenomedullin exerts potent vasodilatory and natriuretic properties which could participate to maintain physiological cardiovascular and renal homeostasis. Whether adrenomedullin is powerful in humans remains to be proven. On the basis of increased plasma levels in hypertension and heart failure, adrenomedullin is suspected to contribute to the pathogenesis of these diseases. A reduced clearance is another possibility but has not yet been investigated in these pathological states. Finally, the ubiquitous distribution of adrenomedullin suggest various other biological activities that need to be established in future.
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PMID:Adrenomedullin: view on a novel vasodilatory peptide with natriuretic properties. 881 9


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