Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of diuretic-induced hyperaldosteronism was examined in dexamethasone-pretreated rats. The diuretic drug frusemide brought about a rapid increase in plasma renin activity and aldosterone concentration in serum. Half an hour after the administration of frusemide the mean concentration of aldosterone was 25 times higher than in vehicle-treated control animals. Administration of SQ 20,881, an inhibitor of angiotensin converting enzyme, prevented the adrenal response to frusemide. The response of aldosterone was completely blocked by indomethacin. This drug reduced renin release and probably also inhibited the effect on the adrenal glands of angiotensin, released in response to frusemide. Our results indicate that the effects of diuretics on the adrenal glomerulosa cells are mediated by the renin-angiotensin system also in the rat. Hyperaldosteronism is dependent on the maintenance of prostaglandin synthesis. ACTH has no essential role in this response.
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PMID:Hyperaldosteronism in the sodium-depleted rat: mode of aldosterone-stimulating action of frusemide. 47 36

A rare case of ACTH-independent Cushing's syndrome due to carcinoma is described. A thirty-year-old woman presented with systolic-diastolic hypertension, unsuccessfully treated for several months with ACE and beta-blockers. During this period physical changes such as centripetal obesity, rubeosis, and hair loss were observed. Elevated urinary and plasmatic cortisol levels were essential for the diagnosis. Alterations of the circadian rhythm with higher levels in the evening compared to the morning were registered. ACTH was found to be suppressed in several tests. Ultrasound and abdominal CT scan showed a mass involving the left adrenal gland. While waiting for surgery, the patient underwent ketoconazole therapy. The operation was carried out by bilateral chest laparotomy and consisted in a left adrenalectomy with regional lymphadenectomy. At 18 months from the operation the patient is in excellent health, the classic signs of Cushing's syndrome have disappeared and laboratory tests are normal.
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PMID:[A case report of Cushing's syndrome due to an adrenal carcinoma]. 158 Nov 62

The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (+/- SD) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 +/- 1.6 micrograms/dl), lowest in 15 control dogs (1.3 +/- 0.5 micrograms/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH; 3.4 +/- 1.2 micrograms/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P less than 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with PDH; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P less than 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 +/- 0.2 microgram/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with PDH, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with PDH failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P less than 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (ACTH).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism. 237 Feb 23

We studied five cases of poorly differentiated follicular or papillary thyroid carcinomas. Immunohistochemical study revealed numerous ACE positive cells, also positive for calcitonin, ACTH, somatostatin or several of these peptides. These tumors containing both vesicular component and parafollicular cells are endocrine tumors of "mixed" or "intermediate" type. The diagnosis must be confirmed by immunohistochemistry but can be suggested by histological findings: abundant fibrous stroma, trabeculovesicular pattern, and swelled moderately acidophilic cells neighbouring vesicular cells. These facts argue in favor of a common-embryological origin of vesicular and parafollicular cells from ultimobranchial undifferentiated cells. Nevertheless such tumors must take place in thyroid neoplasia's classifications and an appropriate terminology remains to be precised.
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PMID:["Mixed' (follicular and parafollicular) carcinomas of the thyroid. Histological and immunocytological study of 5 cases]. 271 68

To investigate whether dopamine plays a role in the regulation of aldosterone secretion during long-term blockade of the renin-angiotensin system, we studied the effect of metoclopramide, a competitive antagonist of dopamine, in 6 patients with essential hypertension chronically treated with the angiotensin converting enzyme inhibitor enalapril. All but one of these patients received a diuretic in addition to enalapril. Six hours after the daily morning dose of enalapril (10-40 mg p.o.) a 10 mg bolus dose of metoclopramide was injected intravenously. In one patient a hypotensive episode developed following metoclopramide administration. In the 5 other patients plasma aldosterone significantly rose within 30 min after metoclopramide from 51 +/- 8.7 to 128.2 +/- 29.2 pg/ml. This metoclopramide-induced release of aldosterone occurred in the absence of concomitant changes in circulating angiotensin 11, potassium and ACTH levels. Metoclopramide given during chronic blockade of the renin-angiotensin system caused anxiety and agitation in 2 patients. The increase in plasma aldosterone following competitive dopamine blockade in the face of chronic angiotensin converting enzyme inhibition, unchanged plasma potassium and ACTH levels strongly suggests that in hypertensive patients, dopamine exerts a direct inhibitory effect on aldosterone secretion.
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PMID:Dopaminergic control of aldosterone secretion in hypertensive patients chronically treated with an angiotensin converting enzyme inhibitor. 300 50

To investigate the role of Angiotensin II in the release of ACTH, the response of adrenocorticotrophic hormone to hypoglycaemia was studied before and during treatment with an angiotensin converting enzyme inhibitor, enalapril, in 15 male patients with essential hypertension. Plasma levels of ACTH were measured before and 60, 90 and 120 min after an i.v. bolus of normal saline, as placebo, and, 3 days later, after an i.v. bolus of regular insulin (0.15 U/Kg b.w.). Enalapril treatment was then started and both placebo and hypoglycaemic tests were repeated 15 days thereafter. No changes in ACTH plasma levels were observed after acute normal saline either before or during enalapril treatment. On the contrary, hypoglycaemia induced a sharp increase of ACTH before enalapril (from 19.5 +/- 4.1 to 74.4 +/- 13.0 pg/ml, p less than 0.01 60 min after insulin) but not during ACE inhibition (from 26.1 +/- 6.2 to 34.6 +/- 5.9 pg/ml, NS, at min 60 of the study). The present data confirm our previous observation on the reduction of the hypoglycaemic-induced ACTH release during ACE inhibition with captopril and support the hypothesis that circulating Ang II may exert a facilitating role on adrenocorticotrophic hormone release.
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PMID:Angiotensin converting enzyme inhibition reduces ACTH release due to hypoglycaemia. 303 30

An enzyme present in mouse brain cytosol cleaves C-terminal dipeptides from substrates including ACTH-(7-10) (Phe-Arg-Trp-Gly), and des-Tyr-[Met]- and des-Tyr-[Leu]enkephalin. By means of ion-exchange chromatography and gel filtration, the peptidase was purified to a specific activity of 1570 times that of brain homogenate. At this purification, a second peptidase, which hydrolyzes Trp-Gly and other peptides [M. E. A. Reith and A. Neidle (1979) Biochem. Biophys. Res. Commun. 90, 794-800] was still present, but could be removed by preparative polyacrylamide gel electrophoresis. The des Tyr-enkephalin-cleaving enzyme has a molecular weight of about 85,000 and a pH optimum of 7.8. It is inhibited by metal-chelating and sulfhydryl reagents. The enzyme has a strong preference for substrates with an aromatic residue in the position adjacent to the C-terminal amino acid, although some peptides meeting this criterion were competitive inhibitors rather than substrates. Peptides with less than four residues were inactive and, in general, tetrapeptides were found to be more reactive than larger analogs, when peptides with common C-terminal sequences were compared. The peptidyl dipeptidase, which has not been described previously, can be readily distinguished from angiotensin-converting enzyme (EC 3.4.15.1) and from neutral endopeptidase (EC 3.4.24.11) by its subcellular localization, substrate specificity, and response to inhibitors. It was suggested that peptidyl dipeptidase-B (PDP-B, EC 3.4.15.-) would be an appropriate name for the enzyme. PDP-B is widely distributed among mouse tissues.
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PMID:The isolation of a peptidyl dipeptidase from mouse brain cytosol that cleaves adrenocorticotropic hormone-(7-10) and des-tyrosine-enkephalins. 608 38

The effect of intravenous injection of the angiotensin converting enzyme inhibitor SQ 14 225 on blood pressure, heart rate and plasma renin concentration (PRC) was investigated in 15 intact conscious ewes as follows: sodium replete during angiotensin I infusion (n = 4); sodium replete (n = 6); sodium deplete (n = 5); chronic water deprivation (n = 5); AcTH treated sodium replete (n = 6). Following SQ 14 225 mean arterial pressure fell 5 +/- 1 mmHg in sodium replete, 20 +/- 4 mmHg in acutely sodium deplete, 7 +/- 2 mmHg in chronic water deprivation and 6 +/- 2 mmHg in ACTH treated sodium replete sheep. This suggests that the renin-angiotensin system plays no significant role in maintaining the elevated blood pressure of sheep with ACTH induced hypertension. Heart rate rose in all groups except the water deprived animals following SQ 14 225. PRC rose from 5.1 +/- 2.1 pmo1AI/ml plasma/h. to 12.4 +/- 2.0 in sodium replete sheep, from 11.9 +/- 1.0 to 68 +/- 13 in acutely sodium deficient animals, and from 13.3 +/- 4.3 to 32.9 +/- 0.6 in chronically water deprived animals, but showed little change in ACTH treated sheep, falling from 2.3 +/- 0.5 to 1.7 +/- 0.2 pmo1AI/ml plasma/h.
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PMID:Effect of angiotensin converting enzyme inhibition with SQ 14 225 on blood pressure in sheep. 625 88

At the present time there is evidence for two families of related peptides which act as ligands for opiate receptor sites. The endorphin group of peptides are derived from the ACTH/LPH precursor pro-opiocortin. The enkephalins appear to be formed from a separate precursor or precursors that have yet to be fully characterized. There appear to be a number of different types of opiate receptors and this may be related to the multiplicity of peptide ligands that have so far been identified. The enkephalins and related peptides appear to have a much wider distribution than the endorphins but the latter may act as circulating hormones unlike the enkephalins. It is likely that both endorphins and enkephalins are involved in sensory modulation processes and release of these peptides has been demonstrated during brain stimulation for pain relief. The enkephalins are very rapidly inactivated by tissue proteases, the aminopeptidases appear largely responsible for the inactivation of exogenously administered enkephalins but the dipeptidyl carboxypeptidase, termed enkephalinase, may have a special inactivating function at enkephalinergic synapses. Evidence will be presented for the biosynthesis, the release and inactivation of the enkephalins relating to the above points.
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PMID:Opioid peptides: aspects of their origin, release and metabolism. 625 71

It is well established that the response of plasma aldosterone to ACTH is enhanced in the sodium depleted state. The mechanisms for this phenomenon are not clear, however, and the present study was undertaken to determine the possible participation of endogenous prostaglandins. ACTH, 250 ug by i.m. administration, was given to 10 human subjects pretreated in four different ways: 1. Control, receiving a 200 mEq per day sodium diet; 2. Sodium depletion (60 mEq/day sodium plus furosemide) plus indomethacin; 3. Sodium depletion plus indomethacin plus captopril; and 4. Sodium depletion plus captopril. Only in the last group, in which the prostaglandin cyclooxygenase inhibitor, indomethacin, was not given during the sodium depletion, did an exaggerated aldosterone response to ACTH occur (an increase of 468% compared with an increase of 182% during control, P less than 0.005). The angiotensin converting enzyme inhibitor, captopril, did not effect this response. Thus, endogenous prostaglandins appear to be of far greater importance than the renin-angiotensin system in mediating the increased aldosterone response to ACTH administration during the sodium depleted state in man.
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PMID:Role of prostaglandins in the aldosterone response to ACTH in sodium depleted human subjects. 629 9


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