Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
 ...
PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

In 15 patients with congenital adrenal hyperplasia, the corticotrophic and melanotrophic functions were evaluated by plasma ACTH and beta-MSH radioimmunoassay. Evaluation of the corticotrophic and melanotrophic functions was also performed in 3 subjects after provocative tests (insulin-induced hypoglycaemia, metyrapone) and in 5 subjects after infusion of synthetic MIF (MSH-release inhibiting factor). The results indicate a significant increase in plasma ACTH and beta-MSH in CAH. In addition, we found that although in most cases there was a significant positive correlation between the plasma ACTH and beta-MSH levels, in some only the plasma ACTH values were high and beta-MSH values normal. No other anomalies of the corticotrophic and melanotrophic functions occurred in CAH as shown by the results of the provcative tests. Lastly, it must be emphasized that no modifications of plasma beta-MSH after synthetic MIF infusion were found in subject with normal or high plasma beta-MSH. These findings induce us to consider it unlikely that synthetic MIF is active in man.
 ...
PMID:Corticotrophic and melanotrophic functions in congenital adrenal hyperplasia. 1 24

Extrapituitary corticotropin-like peptides have been found in central nerves and in gastrointestinal and pancreatic endocrine cells. Previous biological and immunological data strongly indicate that the immunoreactivity present in the central nerves represents corticotropin (A.C.T.H.) or a closely related peptide. In some areas of the brain, the distribution of A.C.T.H. nerves parallels that of nerves containing the endogenous opioid ligand, enkephalin. Since A.C.T.H. fragments bind to the opioid receptor the two neuronal peptides may interact. The antiserum used demonstrates the COOH-terminus of the A.C.T.H. molecule, which is devoid of adrenocortical stimulatory activity. A COOH-terminal A.C.T.H.-peptide, corticotropin-like intermediate peptide (C.L.I.P.), originally isolated from the pars intermedia, has been shown to stimulate release of pancreatic insulin. The presence of C.L.I.P.-like molecules in gut and pancreatic endocrine cells may indicate that C.L.I.P.'s insulin-releasing activity is physiologically important. Further, the occurrence of A.C.T.H.-related molecules in such cells may account for the ectopic A.C.T.H. syndrome associated with some tumours of gut and pancreas.
 ...
PMID:Corticotropin-like peptides in central nerves and in endocrine cells of gut and pancreas. 7 31

Non-insulin-dependent diabetes is associated with facial flushing after alcohol in patients on chlorpropamide (chlorpropamide alcohol flushing, C.P.A.F.) especially when there is a family history of diabetes. C.P.A.F. in three subjects (two diabetics, one non-diabetic) was blocked by the specific opiate antagonist naloxone. In nine subjects (six diabetics) C.P.A.F. was reproduced by the enkephalin analogue with opiate-like activity [D-Ala2, MePhe4, Met (O)-ol] enkephalin (DAMME). C.P.A.F. thus may be due to increased sensitivity to endogenous opiates. DAMME and other substances with opiate-like activity, such as morphine and beta-endorphin, affect carbohydrate metabolism and insulin secretion. Increased sensitivity to endogenous opiates such as enkephalin may thus give rise to non-insulin-dependent diabetes associated with C.P.A.F.
 ...
PMID:Sensitivity to enkephalin as a cause of non-insulin dependent diabetes. 8 99

Adrenocorticotropic hormone (ACTH) inhibited [3H]thymidine incorporation in normal adrenocortical cells of adult rats in culture, with a concomitant increase in corticosterone production and a characteristic retraction of cells. Both dibutyryl cyclic AMP and an analog of ACTH, which produces virtually no cyclic AMP, inhibited DNA synthesis and stimulated steroid production. ACTH inhibited the proliferation of adrenocortical cells obtained from suckling rats as well as the cells obtained from the capsular tissue of adult rat adrenal glands, whereas insulin caused a stimulation of DNA synthesis. These results suggest that the major role of ACTH is to induce the transformation of the undifferentiated cells of the adrenal gland into functional fasciculata cells and that the proliferation of adrenocortical cells may be under control of factors other than ACTH.
 ...
PMID:Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin. 16 10

The effect of synthetic alpha-MSH injected intravenously in a uniform dose of 3 mg was studied in 19 prepubertal children. A marked growth hormone (GH) response was seen only in 2 out of 8 constitutionally small children with a normal GH response to insulin and arginine stimulation. Three of of 11 children suffering from hypopituitarism with documented GH and other hormone deficiencies, unexpectedly, showed a significant rise of GH after alpha-MSH: all three had craniopharyngiomas. Alpha-MSH led to an increase of plasma cortisol in all except 3 patients who had secondary adrenal insuffciency. The increase of cortisol after alpha-MSH and after insulin was of the same extent: but the hypoglycemia and stress responsible for the insulin effect were not observed after alpha-MSH. It is possible that alpha-MSH acts by an ACTH-like direct stimulation on the adrenals. There was no effect of alpha-MSH on plasma TSH or on blood glucose.
 ...
PMID:The effect of alpha-MSH on plasma growth hormone, cortisol and TSH in children. 16 18

The plasma cortisol response to hypoglycemia is widely used as a test of hypothalamic-pituitary-adrenal function. It was the aim of this study to determine whether this test gives a reliable indication of pituitary corticotropin (ACTH) release in patients recovering from adrenocortical suppression due to corticosteroid or ACTH therapy. The 16 patients who were studied (6 on more than one occasion) had received in excess of 5 mg predinisone or equivalent daily for over 12 months. The insulin tolerance tests were carried out 18 h after stopping steroid therapy. The tests were then repeated three to four days after adrenal function had been restored (as indicated by urinary oxogenic steroid excretion of greater than 35 mg/24 h) by zinc tetracosactrin administration. The ACTH response to hypoglycemia was significantly impaired in the steroid-treated group. However with the exception of one patient who had persistently elevated resting ACTH levels there was a significant correlation (P less than 0.01) between the maximum increments in plasma cortisol and ACTH during hypoglycemia. No significant difference in sensitivity to endogenous ACTH could be demonstrated between the steroid-treated group and 12 normal control subjects. Following ACTH administration the plasma ACTH and growth hormone responses to hypoglycemia were significantly reduced, but the response in plasma cortisol was not significantly affected. It is concluded that the plasma cortisol response to hypoglycemia gives a useful indication of ACTH release in steroid-treated patients provided that they have not recently received exogenous ACTH.
 ...
PMID:The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration. 16 25

The effect of alpha1-24-corticotropin-Zn on the results of pituitary stimulation tests (moderate standardized physical exercise, arginine infusion, insulin-induced hypoglycemia) was studied in 27 prepubertal children with non-endocrine retardation of growth and development. After administration of 1 mg alpha1-24-corticotropin, the basal blood glucose and plasma cortisol levels rose significantly. However, the growth hormone increase after the three stimulation tests was significantly lower than without the corticotropin injection. The results demonstrate the inhibiting effect of alpha1-24-corticotropin on growth hormone secretion.
 ...
PMID:The effect of alpha1-24-corticotropin on growth hormone release in prepubertal children. 17 Dec 39

Simultaneous measurements of both beta-melanocyte stimulating hormone (beta-MSH) and adrenocorticotropic hormone (ACTH) in extracted plasma were performed by specific radioimmunoassays. During insulin-induced hypoglycemia, there was a marked increase of plasma ACTH levels and a slight but significant increase of plasma beta-MSH levels. Lysine-vasopressin on the other hand, caused a significant rise of plasma ACTH levels without corresponding response of plasma beta-MSH. Following glucagon administration, neither hormone rose significantly. However, metyrapone infusion caused a significant increase of both ACTH and beta-MSH levels, and frequent blood sampling revealed that both hormones were secreted episodically, and that peaks generally coincided with each other. These data suggest that the secretion of these two hormones can occur together in most instances, and that the same mechanism is involved in the secretion of both hormones under the negative feedback control.
 ...
PMID:Plasma levels of beta-MSH and ACTH during acute stresses and metyrapone administration in man. 17 35

We have obtained direct evidence that shows the cellular formation and subsequent release of a potent inhibitor (feedback regulator) of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by adipocytes, upon stimulation with epinephrine. The appearance of such a feedback regulator in adipocytes preceded its release into the medium. During a 30 min incubation, intracellular regulator levels rose rapidly and reached 39-61 units/g of adipocyte at 10 min. Release of inhibitor into the medium increased slowly and was 11-16 units/g of adipocyte at 10 min. Upon continued incubation, the cells at 30 min contained 30-41 units/g of ingibitor, slightly less than the content at 30 min; meanwhile, the medium content rose more than 3-fold. The inhibitor from both locations appeared to have the same characteristics, judging from the purification procedures and the biological activities on hormone-stimulated adenylate cyclase. Adenylate cyclase was inhibited by the feedback regulator in vitro when either epinephrine, corticotropin (ACTH), or glucagon was used as activator. The site of action of this inhibitor is therefore most likely beyond the specific hormone receptors. A new in vitro action of insulin has been found. Insulin, 50-500 microunits/ml, inhibited the formation and release of this factor from isolated rat or hamster adipocytes by 29-81% after these cells were stimulated by hormones that raise intracellular adenosine 3':5'-cyclic monophosphate. This factor enhaced the effect of insulin in lowering the adenosine 3':5'-cyclic monophosphate levels in fresh rat adipocytes. A reduced formation of such a factor may modify the metabolic events in adipocytes, and some as yet unexplained effects of insulin could therefore be linked to the metabolic effects of this factor.
 ...
PMID:Cellular levels of feedback regulator of adenylate cyclase and the effect of epinephrine and insulin. 17 73


1 2 3 4 5 6 7 8 9 10 Next >>