Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High density lipoprotein (HDL3) binds with high affinity to many types of cells, but controversy exists concerning the nature and biological significance of the binding. We have recently demonstrated that HDL and apoproteins (apo)-AI, -AII, and -CI stimulate a specific and dose-dependent increase in placental lactogen (hPL) release from human trophoblast cells. To examine the possible relationship between HDL3 binding and stimulation of hPL release, we have characterized the binding of [125I]HDL3 to an enriched fraction of hPL-producing trophoblast cells. Binding studies were performed on trophoblast cells isolated by isopycnic centrifugation of collagenase/hyaluronidase-dispersed placental tissue and apo-E free-HDL3 (density, 1.125-1.215 g/ml). Scatchard analysis of binding studies performed at 37 C for 2 h revealed two classes of binding sites: 1) high affinity binding sites with a Kd of 9.7 +/- 2.2 micrograms/ml (1.3 x 10(-7) M) and 9.8 +/- 3.2 x 10(5) binding sites/trophoblast cell, and 2) low affinity binding sites with a Kd of 172.8 +/- 64.8 micrograms/ml (2.3 x 10(-6) M) and an estimated 3.2 x 10(6) sites/cell. As has been found in hepatocytes and other cells, the number of HDL3-binding sites per trophoblast cell (but not the binding affinity) decreased at lower incubation temperatures. In addition, HDL3 binding to trophoblasts cells did not require calcium and was not affected by prior treatment of the cells with pronase or trypsin. HDL3-binding sites on trophoblast cells, however, were not specific for HDL3. Low density lipoprotein (density, 1.063-1.055 g/ml), which does not stimulate hPL release, was nearly as potent on a molar basis as HDL3 in binding to the high and low affinity binding sites on trophoblast cells. Furthermore, nitrated HDL3, which does not compete for high affinity binding to trophoblast cells, stimulated hPL release. Although the characteristics of HDL3 binding to trophoblast cells are similar to those of other cells, these results strongly suggest that the binding of HDL3 to high affinity binding sites is not essential for HDL-mediated hPL release.
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PMID:High density lipoprotein3 binding and biological action: high affinity binding is not necessary for stimulation of placental lactogen release from trophoblast cells. 258 47

The effect of atrial natriuretic peptide (ANP) on renin release is controversial. Several reports state that ANP inhibits renin secretion, while others have shown no effect. We investigated the effect of synthetic rat ANP with 24 amino acids (atriopeptin III) on renin release in vitro in a dynamic superfusion system of renal cortical slices as well as collagenase-dispersed juxtaglomerular cells. In the superfusion system of kidney slices, isoproterenol (5 x 10(-8) M) clearly stimulated renin release from kidney slices, while angiotensin II (AII; 10(-5) M) suppressed renin release. ANP (10(-10)-10(-6) M) did not inhibit basal renin release or blunt the stimulatory effect of isoproterenol. The suppression of renin secretion by AII was never modified in the presence of ANP. The superfusion system of juxtaglomerular cells demonstrated greater sensitivity of renin release in responses to isoproterenol and AII. In this system, ANP (10(-6) M) did not alter renin release from the cells stimulated by isoproterenol (5 x 10(-8) M) or inhibited by AII (10(-8) M). However, basal renin release was slightly stimulated in the late phase of ANP superfusion and for 20 min after the ANP perfusion was stopped. Similarly, 8 bromo-cGMP (10(-6) M) did not inhibit, but, rather, stimulated basal renin release slightly. These results suggest that ANP does not inhibit renin release by a direct effect on the juxtaglomerular cell in the rat.
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PMID:Effect of atrial natriuretic peptide on renin release in a superfusion system of kidney slices and dispersed juxtaglomerular cells. 283 Oct 30

The sites of action of beta-melanocyte stimulating hormone (beta-MSH) on aldosterone biosynthesis were studied using collagenase-dispersed adrenal glomerulosa cells from rats maintained on either normal or sodium-deficient diets for 2 weeks. Isolated cells were treated with a cyanoketone derivative (WIN 19,578) to isolate the early and late steps in aldosterone biosynthesis. WIN 19,578 (1 microM) completely blocked aldosterone production stimulated by sodium depletion, AII, ACTH, and beta-MSH. beta-MSH (1 microM) significantly stimulated pregnenolone production (early step) and the conversion of corticosterone to aldosterone (late step) in aldosterone biosynthesis. The effect of beta-MSH was similar to AII and ACTH. Sodium depletion enhanced the effect of beta-MSH only on the late step in aldosterone biosynthesis. In conclusion, beta-MSH stimulates both the early and late steps of aldosterone biosynthesis. These results suggest that beta-MSH or peptides containing beta-MSH may play a role in the regulation of aldosterone production.
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PMID:Sites of action of beta-melanocyte stimulating hormone in aldosterone biosynthesis in the rat. 298 71

Human adrenocortical tissue obtained, on eight occasions, at the time of nephrectomy for renal carcinoma (outside the adrenal pole) was treated by collagenase to dissociate the cells. These were hen submitted to a short, 2-h, incubation with the N-terminal fragment (16 K) of POMC, its derivative, gamma 3-MSH, beta-lipotropin and beta-endorphin, in parallel with ACTH 1-24 (Synacthen Ciba) and angiotensin II (AII, Hypertensin Ciba). Under the influence of ACTH (10(-10) M), and AII (10(-10) M), basal glucocorticoid output, including more than 80% cortisol, was increased by factors of 3 +/- 0.51 (SEM) and 1.35 +/- 0.12 (SEM), respectively. The corresponding aldosterone responses were 1.60 +/- 0.13 for ACTH and 1.38 +/- 0.09 for AII. With the exception of gamma 3-MSH, the POMC peptides under study had no steroidogenic effect. gamma 3-MSH (10(-9) M) and AII (10(-10) M) stimulated aldosterone production to approximately similar levels of, respectively, 1.23 +/- 0.05 and 1.38 +/- 0.09 times the basal production. In contrast to AII however, gamma 3-MSH showed no apparent effect on glucocorticoid output. Steroidogenic response to ACTH was potentiated by gamma 3-MSH at a concentration of 10(-10) M which, when used alone, proved ineffective. This potentiating effect was pronounced for the aldosterone response, whereas the glucocorticoid production was hardly affected. This action ceased to be visible when the cells reached maximal stimulation by ACTH. These findings suggest that gamma 3-MSH--a portion of the 16 K fragment--may have a possible role in aldosterone secretion.
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PMID:Compared effects of ACTH, angiotensin II and POMC peptides on isolated human adrenal cells. 300 85

The dynamics of the release of human placental lactogen (hPL) under basal conditions and response to various secretogogues has been studied in perifused enriched hPL-producing cells from term placentae prepared by the isopycnic centrifugation of collagenase/hyaluronidase-dispersed placental cells on Percoll gradients. Under basal conditions, the perifused cells released hPL at a relatively constant rate for up to 24 h in culture. The mean rates of hPL release from cells (5 x 10(6) cells) from 18 normal full-term placentae varied from 1.8 to 20.2 ng/5 min (mean 7.7 ng/5 min). The cells from term placentae, however, did not release detectable amounts of chorionic gonadotrophin or the cytosolic enzymes lactic dehydrogenase and alkaline phosphatase. The amounts of hPL released by the perifused cells were inversely related to cell density with mean rates of hPL release by 2, 5, and 10 x 10(6) cells of 15.8, 8.6, and 5.7 ng/10(6) cells/0.5 h. The perifused cells responded to provocative stimuli (high-density lipoproteins (HDL), apolipoproteins AI, AII, and CI, partially purified hPL-releasing factor, phorbol esters, sn-1,2-diacylglycerol, and cAMP) in a manner qualitatively similar to enriched trophoblast cells and placental explants in static culture. Release of hPL in response to HDL, apoproteins AI, AII, and CI, and partially purified hPL-releasing factor was dose-dependent and occurred within 5 min of exposure. Basal and stimulated hPL release by perifused trophoblast cells that had been previously frozen at -70 degrees C for four weeks was identical to that of freshly dispersed cells from the same placenta. These experiments indicate that perifused trophoblast cells may be used as a model system to examine the dynamics of hPL release under basal conditions and in response to provocative stimuli.
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PMID:Characterization of placental lactogen release from perifused human trophoblast cells. 339 89

The steroidogenic properties of a glycoprotein fraction (urinary ASF), isolated from normal human urine, were studied in collagenase-dispersed rabbit adrenal capsular cells in 1) define the requirements for its steroidogenic activity, and 2) assess its site and mode of action. When incubated with adrenal cell suspension at 37 degrees C for 2 hours, urinary ASF induced dose-related increases in both aldosterone and corticosterone production. However, urinary ASF was less potent (ED50 = 10(-9) M) than either angiotensin II (ED50 = 8 x 10(-11) M) or ACTH (ED50 = 4 x 10(-11) M). Increases in cyclic AMP accompanized the steroidogenic response to ACTH but not to either urinary ASF or AII. Deprivation of potassium in incubation media or the addition of ouabain (1 mM) during incubation completely inhibited the steroidogenic response to either urinary ASF, ACTH, or AII. Like ACTH and AII, urinary ASF increased conversion of corticosterone to aldosterone. Specific competitive antagonist of AII (Sar1, Thr8, AII) and ACTH ([I1e9]ACTH1-24) did not prevent the ASF-induced increase in aldosterone production. These results suggest that urinary ASF is readily distinguishable from ACTH. Although it shares similar steroidogenic properties with AII, the inability of AII antagonist to block its effects suggests that it acts at a separate receptor site.
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PMID:Steroidogenic characteristics of a new aldosterone-stimulating factor (ASF) isolated from normal human urine. 626 51

The dopamine antagonist metoclopramide (MCP) has been shown to acutely stimulate aldosterone secretion in vivo. To determine whether a dopaminergic mechanism is involved in the regulation of aldosterone secretion, we examined the effect of minipump infusion of MCP (iv) and/or angiotensin II (AII;sc) upon plasma aldosterone, adrenal capsular AII receptors, and 18-hydroxylase activity in rats maintained on high sodium intake. During normal sodium intake, plasma aldosterone was elevated from 8.3 +/- 1.3 to 35.4 +/- 3.2 ng/dl after 2-day infusion of a nonnatriuretic dose of AII (25 ng/min) and to 15.0 +/- 1.8 ng/dl after the infusion of 1.2 micrograms/min MCP. AII receptors were unchanged by MCP infusion, and rose from 1014 +/- 98 to 1638 +/- 98 fmol/mg after AII infusion. During high sodium intake, the infusion of either AII or MCP alone produced no change in plasma aldosterone or AII receptors. However, after simultaneous infusion of AII and MCP, plasma aldosterone rose from 4.5 +/- 1.2 to 32.5 +/- 2.7 ng/dl, AII receptors increased from 969 +/- 35 to 1607 +/- 280 fmol/mg, and 18-hydroxylase activity, measured as the conversion of corticosterone to aldosterone by isolated mitochondria, rose from 29.5 +/- 1.67 to 40.6 +/- 2.9 pmol/mg . min. These adrenal responses induced by the combined treatment with AII and MCP were similar to the effects of AII infusion during normal sodium intake, indicating that MCP exerts a permissive action upon the trophic effects of AII on the adrenal cell during high sodium intake. These actions of MCP were completely abolished by the simultaneous infusion of dopamine (2 micrograms/min), suggesting that the effects of MCP on adrenal function are due to its dopaminergic antagonist properties. In collagenase-dispersed adrenal glomerulosa cells, only supraphysiological concentrations of dopamine in the incubation medium (10-100 microns) inhibited basal, AII-stimulated, and ACTH-stimulated aldosterone production, and these inhibitory effects were not reversed by high concentrations of MCP. Also, MCP itself inhibited both basal and stimulated aldosterone production. These results suggest that the stimulatory actions of MCP in vivo are exerted through liberation of other local regulators, rather than directly upon the adrenal glomerulosa cell. These findings have defined a mechanism by which the primary regulatory action of AII upon aldosterone secretion can be modulated during high sodium intake by dopaminergic inhibition of adrenal glomerulosa function.
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PMID:Dopaminergic modulation of aldosterone secretion in the rat. 631 44