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)

Cells obtained by continuous perfusion with collagenase maintained their ultrastructure and their capacity for protein synthesis in contrast to mechanically isolated rat liver cells. Albumin and angiotensinogen (renin substrate) are synthesized and secreted and the synthesis of both proteins is stimulated by addition of hydrocortisone. As cell suspensions allow the simultaneous investigation of several samples under well defined conditions they can serve as an excellent model for the study of regulatory mechanisms of serum protein synthesis.
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PMID:[Blood protein synthesis in isolated liver cells]. 19 70

The age-related changes in the morphology and function of rat adrenal zona glomerulosa (ZG) were investigated by coupled stereological and radioimmunological techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Aging caused a notable lowering in the plasma aldosterone concentration and a marked decrease in both basal and ACTH- or angiotensin II (ANG-II)-stimulated secretion of collagenase-dispersed ZG cells. Plasma renin activity (PRA) underwent an age-dependent decrease, while the plasma level of ACTH displayed a significant rise. ZG and its parenchymal cells did not evidence any age-related morphologically demonstrable alteration in their growth, nor ZG cells showed any marked ultrastructural change, with the exception of a severe lipid-droplet repletion. This last finding is in keeping with the aging-induced decrease in the secretory activity of ZG cells, inasmuch as lipid droplets are the intra-cellular stores of cholesterol esters, the obligate precursors of steroid hormones in rat adrenals. ACTH and ANG-II are well known to be involved in the maintenance of the growth of rat ZG; thus, the combined impairment of ANG-II production (as evidenced by PRA lowering) and increase in ACTH secretion may maintain unchanged ZG growth during aging.
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PMID:Age-related changes in the morphology and function of the zona glomerulosa of the rat adrenal cortex. 148 25

The kidney and parathyroid gland play key roles in calcium (Ca++) homeostasis. Recent data suggest that the kidney, in addition to being a primary target for PTH, also recognizes changes in the concentration of extracellular Ca++, thereby modulating hormone-dependent cAMP production, 1,25-dihydroxyvitamin D synthesis, and renin secretion. In this study, we examined: 1) the effects of varying concentration of divalent cations on PTH-dependent cAMP production in renal proximal tubular cells; and 2) the mechanisms by which extracellular Ca++ exerts its inhibitory effects on cAMP production. Single cell suspensions composed of 80-90% proximal tubular cells were prepared from cortical homogenates by collagenase digestion and sieving. In the presence of 1 mM isobutylmethylxanthine, cAMP content was measured by RIA in 5-15 min incubations and showed a 5- to 6-fold increase in response to PTH (10(-11) -10(-6) M). Increasing extracellular Ca++ and magnesium (Mg++) from 0 and 0.5 mM, respectively, to 5.0 mM inhibited PTH-dependent (3 x 10(-9) M) cAMP production by 54 +/- 4% and 47 +/- 6%, respectively. The half maximal inhibitory concentration for both Ca++ and Mg++ was 0.9 mM. In addition, increasing extracellular barium (Ba++) or strontium (Sr++) from 0-10 mM inhibited PTH-dependent (3 x 10(-9) M) production by 54 +/- 7% and 62 +/- 6% with half of the maximal observed inhibition at 2.2 and 2.7 mM, respectively. The inhibition of PTH-dependent cAMP production by 2.5 mM Ca++ was not reversed by the calcium channel blockers diltiazem or verapamil (10(-4) M). However, changes in intracellular calcium may play some role in the inhibitory effects of Ca++ on cAMP production, since ionomycin (10(-6)-10(-5) M) lowered PTH-dependent cAMP production by 25-36%. Our data suggest that the proximal tubular cell can sense physiologically relevant changes in Ca++, providing a potential mechanism for the modulation of 1,25-dihydroxyvitamin D production or other tubular functions relevant to fluid and mineral homeostasis.
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PMID:Divalent cations modulate PTH-dependent 3',5'-cyclic adenosine monophosphate production in renal proximal tubular cells. 164 58

Renin gene expression in the mouse kidney and submandibular gland (SMG) are differentially regulated by cAMP. In this study, we examined the potential molecular mechanism responsible for this tissue-specific regulation. 32P end-labeled synthetic oligonucleotide containing mouse renin cAMP-responsive element (CRE) was incubated with kidney nuclear extracts from either control or cAMP-treated mice and analyzed by gel mobility shift assay. Our results demonstrated that cAMP induced a nuclear protein which complexed with the CRE oligonucleotide in a specific manner. This nuclear protein-DNA binding was competed effectively by the oligonucleotide containing human chorionic gonadotropin alpha-subunit CRE but not by the mouse renin DNA fragment from which the CRE was deleted by site-directed mutagenesis. In contrast, no DNA-protein complex formation could be detected when this [32P]CRE oligonucleotide was incubated with the SMG nuclear extract from control or cAMP-treated mice. However, CRE-binding protein complex formation was demonstrated in the SMG nuclear extract when the incubation was performed in the presence of 0.8% sodium deoxycholate and 1.2% Nonidet P-40, detergents that dissociate protein-protein complexes. Furthermore, in the absence of deoxycholate, we observed that SMG nuclear extract attenuated the binding of the kidney CRE-binding protein to mouse renin CRE in a dose-dependent manner and this inhibitory effect of SMG nuclear extract disappeared in the presence of sodium deoxycholate. This inhibitory nuclear protein in SMG is specific for CRE-binding protein since it does not affect nuclear protein binding to synthetic DNA oligonucleotides of human collagenase AP-1 and human metallothionein AP-2. Our data further suggest that inhibitory nuclear protein is present in lower quantities in other extrarenal tissues, i.e. testes, liver, brain, heart, but is not detectable in the kidney. Taken together, these results suggest that the SMG and certain extrarenal tissues contain nuclear trans-acting factor(s) that interact with CRE-binding protein, thereby interfering with its binding to mouse renin CRE. The presence of this inhibitory protein in the mouse SMG nucleus may contribute to the tissue-specific regulation of the renin gene expression by cAMP.
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PMID:Molecular mechanism of tissue-specific regulation of mouse renin gene expression by cAMP. Identification of an inhibitory protein that binds nuclear transcriptional factor. 165 39

This study assessed the effect of chronic infusions of atrial natriuretic factor (ANF) on in vivo and in vitro production of aldosterone. Vehicle (saline) or rat ANF-(99-126) was intravenously infused at 100 ng.kg-1.h-1 for 5 consecutive days into male New Zealand White rabbits. At 5 days plasma ANF was 18 +/- 4.1 pg/ml in vehicle-infused and 48.5 +/- 9.0 in ANF-infused rabbits (P less than 0.01). Plasma renin activity was significantly less in ANF-infused rabbits (2.99 +/- 0.35 vs. 0.77 +/- 0.12 ng.ml-1.h-1, P less than 0.01); however no differences were observed in the basal plasma concentrations of aldosterone, corticosterone, potassium, or hematocrit. In in vivo studies, chronically administered ANF attenuated plasma aldosterone, but not pressor, responses to acutely infused angiotensin II given at doses of 4, 16, and 64 ng.kg-1.min-1 for 20 min each. In in vitro experiments, collagenase-dispersed adrenal capsular cells from ANF-infused rabbits exhibited significantly reduced maximal responses to adrenocorticotropic hormone, angiotensin II, and potassium. These results suggest that chronic small increases in circulating ANF can blunt selectively adrenocortical responses to aldosterone secretagogues without affecting pressor responses to angiotensin II.
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PMID:Impaired aldosterone production by long-term infusion of atrial natriuretic factor. 213 94

Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.
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PMID:The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis. 216 17

1. The role of Ca2+ in the control of renin release was investigated using a collagenase-dispersed rat kidney cortex cell preparation. 2. Superfusion with a series of low [Ca2+] buffers in either ascending or descending order of concentration increased renin release. Exposure to 0.06 mmol/l Ca2+ increased release by 120% (P less than 0.001) when presented as the first buffer in ascending order of concentration and by 79% (P less than 0.001) when presented as the fourth and last in a series of descending order. 3. The Ca2+ entry blocking drug diltiazem in a range of concentrations increased renin release and at 10(-5) mol/l diltiazem the mean stimulation was 35% (P less than 0.01). 4. 8-(N.N-Diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) reduces the release of Ca2+ from intracellular stores and, studied over a range of concentrations, this compound increased renin release. At 10(-5) mol/l TMB-8 the mean increase was 44% (P less than 0.001). 5. None of these experimental manipulations, low [Ca2+], diltiazem or TMB-8, had any effect on the release of adenosine 3':5'-cyclic monophosphate into the cell superfusate, indicating that a decrease in intracellular [Ca2+] increases renin release by a mechanism which is independent of changes in adenosine 3':5'-cyclic monophosphate production. 6. Effects of low [Ca2+], diltiazem and TMB-8 on renin secretion were all shown to be reversible when superfusion with control buffer was resumed.
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PMID:Inhibitory role of Ca2+ in the control of renin secretion: a study using superfused dispersed rat renal cortical cells. 255 24

We previously reported that endothelin inhibits renin release in a dynamic superfusion system of collagenase-dispersed rat renal cortical cells. In the present report we investigated cellular mechanisms by which endothelin inhibits renin release from juxtaglomerular (JG) cells. In a superfusion system of dispersed rat renal cortical cells, 10(-10) M endothelin inhibited renin release stimulated by 5 x 10(-8) M isoproterenol or 5 x 10(-5) M 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8, a putative intracellular Ca antagonist). Endothelin showed a slight but significant inhibitory effect on renin release stimulated by isoproterenol or TMB-8 even in the absence of extracellular Ca. Endothelin also inhibited renin release in the presence of 10(-4) M nicardipine. In a superfusion system of renal cortical slices, both 10(-8) M endothelin and a high concentration (60 mM) of K inhibited renin release, and 10(-6) M nicardipine attenuated the inhibition of renin release by high K but did not affect the inhibition by endothelin. These results suggest that endothelin inhibits renin release from JG cells not only by the promotion of Ca influx into the cells through dihydropyridine-insensitive Ca channels but also by other mechanism(s) independent of extracellular Ca.
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PMID:Inhibitory effect of endothelin on renin release in vitro. 269 55

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

Adrenocortical function was assessed in six normal and six chronic (greater than 12 weeks), DOCA-hypertensive Yucatan miniature swine; mean arterial pressures were 115.3 +/- 11.7 and 163.6 +/- 27.2 mm Hg, respectively (mean +/- SEM). Adrenocortical function was evaluated in vivo by measuring changes in plasma cortisol and aldosterone in response to exogenous ACTH (0.25 mg, iv), and in vitro by measuring the responses of collagenase-isolated adrenocortical cells to ACTH and angiotensin II. Corticoids were measured by specific radioimmunoassay. Basal plasma cortisol values of conscious DOCA-hypertensive swine were approximately 53% of the values of normotensive swine (P less than 0.05). However, ACTH induced a 419% increase in plasma cortisol values in DOCA-hypertensive swine compared to a 261% increase in the normotensive swine (P less than 0.05). These differences between the two groups were not altered by anesthesia. There were no significant differences in ACTH-induced changes in plasma aldosterone between the normotensive and DOCA-hypertensive swine. Experiments in vitro showed that the corticoid secretory responses of adrenocortical cells from DOCA-hypertensive animals were 6 times more sensitive to ACTH and 3.2 times more sensitive to angiotensin II than those of cells from normotensive swine. Thus, despite the possibility of adrenocortical insufficiency due to suppressed plasma renin activity and the negative feedback of DOCA on the hypothalamic-hypophyseal-adrenal axis, adrenocortical function of DOCA-hypertensive swine was hyperresponsive to trophic hormones. Results from this study suggest that the DOCA-hypertensive swine may be a valuable model in elucidating the relationship between hypertension and adrenocortical function and in investigating nonclassical control of the adrenal cortex, that is, control exerted during the hypertensive state that exists apart from or in addition to that exerted by ACTH and angiotensin II.
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PMID:Adrenocortical function in deoxycorticosterone acetate (DOCA)-hypertensive Yucatan miniature swine. 298 91


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