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)

In a placebo-controlled, randomized, crossover, double-blind study of 17 normal volunteers, we examined the effects of captopril on the concentration of opioid peptides during bicycle exercise and on quality of life after a 2-week treatment period. Two exercise tests (progressive exercise and constant work rate exercise) were performed. Maximum oxygen uptake and blood lactate concentrations were measured in progressive exercise tests. The exercise intensities corresponding to a 1/2 lactate threshold, a lactate threshold, and a 4 mmol/L lactate concentration were determined. Constant work rate exercise at selected work loads for 20 minutes was carried out to measure the concentrations of opioid peptides and other hormones. Quality of life was assessed after the 2-week treatment period. Captopril treatment had no effect on the exercise response of blood pressure, heart rate, maximum VO2, and maximum work loads. The plasma concentrations of lactate, epinephrine, norepinephrine, and aldosterone increased during exercise and captopril did not change them. Beta-endorphin levels and plasma renin activity also increased during exercise, and the increases were greater with captopril treatment. Met-enkephalin and leu-enkephalin concentrations did not increase during exercise. According to responses in the quality of life questionnaires, administration of captopril improved the physiologic state more than the placebo did. These findings suggest that captopril may act on the central nervous system involving an increase in the beta-endorphin level.
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PMID:Effects of captopril on opioid peptides during exercise and quality of life in normal subjects. 195 Oct 4

We investigated the possibility that angiotensin II (ANGII) augments the sensitivity of the pituitary to corticotropin releasing factor (CRF) by comparing, in patients with essential hypertension, the responses of plasma adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin activity to a bolus injection of either 0.5 or 1.0 microgram/kg of synthetic ovine CRF in control conditions and after chronic treatment with the converting enzyme inhibitor captopril to block the formation of ANGII; the effects of CRF were examined up to 4 h after its administration. In control studies, we found that the two doses of CRF induced similar increments in ACTH and cortisol, the levels of which remained elevated throughout the studies; these changes were associated with increments in plasma aldosterone that were dose dependent, less pronounced, and of shorter duration and with a slight decrease in plasma renin activity. Captopril treatment increased basal plasma renin activity and lowered plasma aldosterone while leaving basal ACTH and cortisol unchanged. During converting enzyme inhibition, the responses of ACTH and cortisol to CRF were similar to those observed in control studies, whereas the changes in plasma aldosterone and plasma renin activity were, respectively, smaller and greater. From these results, it appears that during ANGII blockade the sensitivity of ACTH to CRF stimulation is unaffected, whereas that of the adrenals to ACTH is selectively reduced at the level of the zona glomerulosa.
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PMID:Effects of angiotensin II blockade on the responses of the pituitary-adrenal axis to corticotropin-releasing factor in humans. 248 58

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.
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PMID:Hormonal and renal responses to converting enzyme inhibition during maximal exercise. 282 83

Haemodynamic and humoral effects of captopril were studied in patients with essential and renovascular hypertension. Captopril decreased significantly both systolic and diastolic blood pressure and moderately, it reduced also the heart rate. On the basis of the haemodynamic effects our patients could be divided into two groups: in patients where the total peripheral resistance (TPR) exceeded 2000 dyn x sec x cm-5 during rest, captopril exerted its hypotensive effect by decreasing TPR. In patients in whom TPR was lower, the hypotensive action could be attributed to the reduction of cardiac output (CO). Captopril increased plasma renin activity, and decreased the activity of angiotensin converting enzyme (ACE) in the plasma. In acute study captopril did not influence plasma noradrenaline level but increased it during long-term administration. It did not affect dopamine or adrenaline levels. Captopril had no effect on plasma beta-endorphin concentration, moreover, the opiate antagonist, naloxone, failed to antagonize its antihypertensive effect. Comparing the acute effects of Capoten (Squibb, USA) and Tensiomin (EGIS, HUNGARY) no significant differences were found.
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PMID:Clinical studies with captopril treatment of hypertensive patients. 285 93

Endogenous opioid peptides, by modulating the release of sympathetic transmitters, may play a role in the pathogenesis of migraine and related headaches which are considered hypernociceptive syndromes. Hypoendorphinaemia has been demonstrated in migraine attack. Captopril, a drug able to potentiate morphine analgesia in rats and inhibit enkephalinase in animals and in man, improves the clinical course of migraine. In the present research the cerebrospinal fluid and plasma beta-endorphin (beta-EP) levels have been evaluated following a single oral dose of captopril. The drug increased plasma beta-EP levels in migraine sufferers, and these data may be relevant in the mechanism of action of this drug in migraine and related headaches.
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PMID:Hypernociceptive syndromes and pharmacological inhibition of endogenous opioid degradation. 294 84

The generation of met-enkephalin (Tyr1-Gly2-Gly3-Phe4-Met5) from met-enkephalin-Arg6-Phe7 and subsequent degradation of the liberated peptides to the free amino acids by rat brain cortical synaptosomes in vitro was demonstrated by HPLC and amino acid analyses. Kinetic measurements of the individual steps of met-enkephalin processing and degradation upon incubation with synaptosomes revealed the following sequence of cleavage: 1. Hydrolysis of the Met5-Arg6 peptide bond, generating met-enkephalin and the dipeptide Arg-Phe. Captopril and EDTA inhibit this reaction. 2. Hydrolysis of the Tyr1-Gly2 peptide bond, generating Tyr and a tetrapeptide. Puromycin (ID50 = 5 X 10(-5) M) and parahydroxymercuribenzoate (ID50 = 5 X 10(-4) M) inhibit this reaction. 3. Hydrolysis of the Gly3-Phe4 peptide bond. Parahydroxymercuribenzoate (ID50 = 5 X 10(-4) M) inhibits this reaction completely. 1 mmol liter-1 Puromycin does not inhibit this reaction. 4. Hydrolysis of the Phe4-Met5 peptide bond. 5. Hydrolysis of the Gly2-Gly3 peptide bond. The pH optimum of all cleavage reactions was found to be around 7.8.
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PMID:Processing and degradation of met-enkephalin by peptidases associated with rat brain cortical synaptosomes. 635 99

It has been previously shown that endogenous opioid peptides suppress human ACTH and gonadotropins secretion via hypothalamic mechanism. Since the angiotensin converting enzyme can participate in the metabolism of opioid peptides, this study examined the action of Captopril, an angiotensin converting enzyme inhibitor, on corticotropin and gonadotropin (LH and FSH) release induced by the opiate antagonist naloxone in man. Seven male hypertensive volunteers (aged 30-52) were treated with A) saline; B) naloxone 8 mg iv as a bolus followed by an iv infusion of 4 mg/h; C) naloxone as above after pretreatment with captopril 150 mg/day for 15 days; D) captopril alone. Naloxone significantly stimulated ACTH and LH secretion when compared with the saline infusion. This stimulating effect was taken as an indirect evidence for a tonic opioid inhibition on pituitary hormones release. The pre-medication with captopril significantly enhanced the ACTH and LH response to the opiate antagonist naloxone, but captopril alone did not modify ACTH and LH values when compared to saline. The results would suggest that captopril interferes with the opioid regulation of human ACTH and LH secretion probably by blocking the proteolytic degradation of opioid peptides.
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PMID:Effect of captopril, an inhibitor of the converting enzyme on naloxone induced secretion of ACTH and LH in man. 826 63

The present study was carried out to elucidate whether an exercise-induced increase in plasma hydrogen ion concentration influences aldosterone secretion. Six healthy men (aged 22-25 years) performed two intermittent exercise tests with and without drug administration. The intensities of these exercise tests were 40% maximal oxygen uptake (VO2max) and 90% VO2max, respectively. Administration of 2-mg Dexamethasone and 50-mg Captopril caused an almost complete suppression of adrenocorticotropic hormone (ACTH) and an enhancement of the elevation in renin concentration during exercise, indicating successful inhibition of ACTH release and angiotensin II production during exercise. While the magnitude of the increase in aldosterone in the drug experiment was depressed compared with the control experiment, a significant increase in aldosterone concentration was observed at the end of the 90% VO2max exercise. Whilst the change in aldosterone concentration did not correlate with the change in plasma potassium concentration, there was a significant correlation between aldosterone and plasma hydrogen ion concentrations in the drug experiment. Since the correlation coefficient was low (r = 0.455), the biological meaning of this correlation should be further investigated. These results would suggest that an elevation of plasma hydrogen ion concentration induced by exercise per se appears to be related, at least in part, with increased aldosterone secretion, independent of the pituitary-adrenal axis, and the renin-angiotensin system.
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PMID:Effect of exercise-induced acidosis on aldosterone secretion in men. 956 90

We studied the effect of alterations in the intake of sodium and potassium as well as changes in circulating adrenocorticotropin (ACTH) on the expression of the two rate-limiting systems of aldosterone formation in the rat. Low sodium and high potassium intake promoted time-dependent increases in the zona glomerulosa cytochrome P450scc (P450scc) and cytochrome P450c11 (P450c11) protein and mRNA levels, but no changes were found in the zona fasciculata-reticularis. In addition, these responses were associated with markedly elevated transcriptional activities. To further define the contribution of P450c11 and P450c18 (aldosterone synthase) in response to these differing intakes, we evaluated their mRNA levels using gene-specific oligonucleotide probes. P450c18 mRNA was restricted to the zona glomerulosa, whereas P450c11 mRNA was detected in both zona glomerulosa and zona fasciculata-reticularis. Furthermore, only P450c18 mRNA was induced by both low sodium or high potassium intake, as P450c11 mRNA levels remained unchanged. Captopril, an inhibitor of angiotensin-I converting enzyme, abolished the enhancing effects of the low sodium regimen on P450scc and P450c18 mRNA levels. Captopril also suppressed the augmentation of P450c18 mRNA observed with potassium supplementation but had no effect on P450scc mRNA levels. When the hypocholesterolemic drug 4-aminopyrazolopyrimidine (4-APP) was administered to rats for 3 consecurive days, both the level of plasma ACTH and the adrenal content of mRNA encoding P450scc increased 24 h post final injection. The coadministration of dexamethasone with 4-APP prevented these increases. In contrast, the mRNA content of P450c11 remained at control levels. In conclusion, this work demonstrates that variations in the intake of sodium and potassium act on the expression of the CYP11B2 gene, but not on that of the CYP11B1 gene. Moreover angiotensin-II (A-II) is an important factor in this mechanism of action. Both ions also enhance the expression of the CYP11A1 gene. A-II appears to participate in the mechanism of action of the low sodium intake at this level. Another mechanism is postulated for the action of potassium supplementation since captopril did not prevent the increased expression of the CYP11A1 gene. In addition, the fact that 4-APP enhanced the mRNA level of P450scc but not that of P450c, also demonstrates different regulation of the P450s involved at the early and final steps of aldosteroone formation in the rat adrenal zona glomerulosa in vivo.
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PMID:In vivo regulation of gene expression of enzymes controlling aldosterone synthesis in rat adrenal. 2221 27