Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholera enterotoxin, 45 mug per 250 g body weight, administered intravenously to rats, caused a 6-fold rise in the activity of liver alkaline phosphatase in 12 hr. There was no change in bile volume or in the concentration or total bile content of Na+, K+, HCO3-, or Cl- for 36 hr after the administration of cholera toxin. However, bile phospholipid output fell markedly from a control level of 15.0 +/- 1.0 mumol per 6 hr to a low level of 4.0 +/- 1.2 mumol per 6 hr in the 12- to 18-hr collection, P less than 0.001. There was a similar fall in bile acid secretion, from a control value of 9.8 +/- 0.4 mumol per 6 hr to 4.1 +/- 0.9 mumol in the 12- to 18-hr period, P less than 0.01. The cholera effect was prolonged. Bile acid and phospholipid secretion rates did not return to control values until 30 to 36 hr after the administration of cholera enterotoxin. The cholera toxin-induced reductions in bile acid and phospholipid secretion into bile did not appear to be mediated by adenyl cyclase or cyclic AMP because neither glucagon, a known stimulator of liver adenyl cyclase, nor dibutyryl cyclic AMP had any effect on the secretion into bile of bile acids or phospholipid. The administration of cholera toxin was not associated with any increase in the secretion of free choline into bile. Glucagon and dibutyryl cyclic AMP, two other substances known to increase the activity of rat liver alkaline phosphatase, also had no stimulatory effect on the secretion of free choline into bile. The results do not support the hypothesis that the main function of rat liver alkaline phosphatase is to facilitate the excretion of free choline into bile.
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PMID:Effects of cholera enterotoxin, glucagon, and dibutyryl cyclic AMP on rat liver alkaline phosphatase, bile flow, and bile composition. 17 82

We studied the effect of bromolevamisole (BL) and other imidazo [2,1-b] thiazole derivatives--bromodexamisole (BD) and levamisole (LV)--on adenylate cyclase (AC) activity. BL and BD both inhibited forskolin-activated human thyroid AC, while LV had no effect. This inhibition was non-stereospecific and the IC50 values, as measured with 1 mM ATP and 40 microM forskolin, were 0.95 and 0.80 mM for BL and BD, respectively. In contrast, human thyroid alkaline phosphatase (ALP) inhibition was stereospecific, with IC50 values of 0.0012 mM for BL and 0.9 mM for BD. LV was a 10-fold weaker inhibitor of ALP than BL. These results show that ALP inhibition is not correlated with forskolin-activated AC inhibition. Furthermore, in the presence of a competitive inhibitor of GTP (0.1 mM guanosine 5'-O-(2-thiodiphosphate), BL retained its antagonizing effect on forskolin-activated AC which suggests a direct action on the catalytic subunit. The inhibition was of the mixed type, indicating a complex interaction between BL and AC. Glucagon-activated AC activity in rat liver membranes was also inhibited by BL, although to a slightly lesser degree than thyroid stimulating hormone (TSH)-activated AC from human thyroid for a given BL concentration. In cultured human thyroid cells, BL (0.25 mM) induced a potent decrease in cAMP accumulation after 2 hr of stimulation by TSH. Taken together, these results show that BL inhibits AC and that this inhibition is not organ-specific.
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PMID:Effect of bromolevamisole and other imidazo [2,1-b] thiazole derivatives on adenylate cyclase activity. 131 3

The regulation of different maturational processes in the liver is believed to be influenced by the hormonal system. The aim of this study was to investigate the effect of two hormones, glucagon and dexamethasone, on levels of plasma membrane proteins in rat liver cells during late fetal and early postnatal stages of development. For this purpose, 18-day-old rat fetuses and 1-day-old newborns were treated with glucagon or dexamethasone and killed at 22 days of gestation and 3, 5 and 7 days of age, respectively. Postnuclei liver membranes were isolated using a sucrose gradient method and assessed for levels of specific membrane proteins. Asialoglycoprotein receptor and 110,000 Mr glycoprotein, denoted GP 110, representing the sinusoidal and bile canalicular domains, respectively, were quantitated using the immunoblot method. Membrane enzymes alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transferase were evaluated using enzymatic methods. The data showed that glucagon and dexamethasone have a differential effect on membrane constituents according to the stage of development. Glucagon increased the levels of membrane enzymes during the late fetal stage but had no effect on liver membrane proteins in the newborn animal. In contrast, although dexamethasone elevated GP 110 in fetal rat livers, none of the other marker proteins was significantly affected. On the other hand, in newborns dexamethasone reduced the amount of asialoglycoprotein receptor and alkaline phosphatase and leucine aminopeptidase enzyme activities but greatly augmented the level of gamma-glutamyl transferase. Thus, glucagon primarily affects plasma membrane proteins in late gestation while dexamethasone does so during the early postnatal period. The roles that these two hormones may play during ontogeny is discussed with respect to liver development.
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PMID:The effect of dexamethasone and glucagon on the expression of hepatocyte plasma membrane proteins during development. 289 49

Glucagon given by intravenous infusion at a dosage of 0.2 to 0.8 mg/hour to four patients with Paget's disease of bone resulted in a dramatic fall in plasma alkaline phosphatase. This was associated with a fall in 24-hour urinary calcium and in total urinary hydroxyproline excretion and a marked relief of bone pain.GLUCAGON MAY INDUCE THESE CHANGES BY THREE POSSIBLE MECHANISMS: (1) by stimulating release of calcitonin; (2) by a direct action of the hormone on bone; and (3) by stimulation of certain bone pyrophosphatases, thus altering the local mechanisms controlling the rate of bone formation and resorption.
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PMID:Glucagon in the treatment of Paget's disease of bone. 512 17

Paired indirect immunoenzyme staining based on primary antisera from the same species was performed sequentially without intermediate antibody elution. The first antigen was labelled brown by an immunoperoxidase procedure (either the two-stage indirect method, the unlabelled antibody peroxidase-antiperoxidase method, or the avidin-biotin bridge method using diaminobenzidine (DAB) and hydrogen peroxide as the substrates. The second antigen was labelled blue by applying a two-stage indirect immuno-alkaline phosphatase procedure using naphthol AS phosphate and Fast Blue BB salt as the substrate. In this way, polyclonal mucosal immunocytes were revealed in distinctly contrasting colours when stained for kappa and lambda light chains. Glucagon and somatostatin (D) cells in human pancreatic islets, and gastrin and D cells in human gastric antral glands, were likewise clearly differentiated. Conversely, a mixed colour appeared in some immunocytes after staining for alpha and kappa chains. However, unbalanced colour mixing was sometimes difficult to interpret, and additional experiments demonstrated that unwanted interactions could take place between the two sequences of reagents if the density of the DAB deposits was insufficient. These pitfalls were incompatible with unequivocal double staining in the same cell. Nevertheless, paired staining could be conveniently applied with the described procedures when prior knowledge had established that the antigens in question were located in separate cells.
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PMID:Paired indirect immunoenzyme staining with primary antibodies from the same species. Application of horseradish peroxidase and alkaline phosphatase as sequential labels. 620 74

Glucagon has been shown to lower blood lipids and to decrease food intake and body weight in short-term studies in man and animals. There is evidence of decreased secretion of glucagon in human obesity. The Zucker obese rat suffers from a genetic type of obesity and has an absolute reduction in circulating glucagon concentration. The effect of long-term administration of glucagon on the body weight in obese Zucker rats was studied. Glucagon caused a marked (-20%) reduction of body weight in obese Zucker rats with no change in feed intake. Urine glucose, urea nitrogen, creatinine, and ketone content, as well as serum triglyceride, cholesterol, alkaline phosphatase, creatinine, and insulin levels remained unchanged. Weights of perirenal fat, kidneys, and heart also remained unchanged. However, glucagon injection in obese Zucker rats caused significant decrease in serum glucose, and increases in SGOT, liver weight, and liver lipid and glycogen content. Further investigations are needed concerning the safety of chronic glucagon administration for weight control.
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PMID:Suppression of weight gain by glucagon in obese Zucker rats. 672 36

This study was done to determine glucagon's effect on protein biliary excretion in anesthetized, bile duct-cannulated guinea pigs. Glucagon (1.4 nmol.min-1.kg-1) induced choleresis and increased protein biliary concentration from 0.12 +/- 0.04 to 0.20 +/- 0.6 mg/ml and protein output from 22.8 +/- 3.8 to 54.5 +/- 16.1 micrograms.kg-1.min-1. Protein biliary excretion increased during the first 10 min of glucagon infusion and progressively declined thereafter. Biochemical analysis of biliary protein revealed that the increase could be accounted for primarily by an increase in the lysosomal enzymes acid phosphatase and beta-glucuronidase. Biliary excretion of the canalicular membrane enzymes 5'-nucleotidase and alkaline phosphatase only modestly increased, whereas that of [14C]sucrose, a marker of paracellular fluid transport, was unaffected. On the other hand, glucagon enhanced biliary entry of horseradish peroxidase in a fashion similar to that observed with total endogenous protein. These effects were mediated by the adenosine 3',5'-cyclic monophosphate (cAMP) system, since infusion of dibutyryl-cAMP at 0.5 mumol.kg-1.min-1 increased bile flow and biliary protein excretion in a time-dependent manner, as observed with glucagon. Glucagon's failure to sustain enhanced protein biliary output was not due to declining hepatic concentrations of cAMP or to depletion of hepatocellular lysosomal enzymes. These studies provide evidence that glucagon stimulates biliary excretion of protein in guinea pigs that can be accounted for by biliary discharge of enzyme originating from the canalicular membrane and, primarily, from the lysosomal compartment. Although the precise mechanism(s) underlying these effects remains to be elucidated, it is suggested that the increase in canalicular membrane enzyme excretion is due to glucagon's effect on exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon induces biliary protein excretion in guinea pigs. 838 43

Glucagon-like peptide-1 (GLP1) and its receptor agonist have been previously reported to play a positive role in bone metabolism in aged ovariectomized rats and insulin-resistant models. However, whether GLP1 has a direct effect on the proliferation and differentiation of osteoblasts or any cellular mechanism for this potential role is unknown. We examined the effects of the GLP1 receptor agonist exendin-4 on the proliferation, differentiation, and mineralization of mouse osteoblastic MC3T3-E1 cells. GLP1 receptor was detected in MC3T3-E1 cells by polymerase chain reaction (PCR) and Western blot assay. Cell proliferation was assessed using MTT assay, revealing that exendin-4 increased cell proliferation at effective concentrations between 10(-10) and 10(-5) M. Quantitative PCR analysis showed that exendin-4 increased the mRNA expression of the differentiation markers alkaline phosphatase (ALP), collagen-1 (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2) under osteogenic conditions. Alizarin red staining confirmed that 10(-7) M exendin-4 increased osteoblast mineralization by 18.7%. Exendin-4 upregulated the phosphorylation of ERK1/2, p38, and JNK, with the peak effect at 1.5 h in the Western blot analysis. The use of selective MAPK inhibitors, namely PD98059, SB203580, and SP600125, blocked the effects of exendin-4 on kinase activation (ERK1/2, p38, and JNK), as well as cell proliferation and differentiation in MC3T3-E1 cells. These findings demonstrate that exendin-4 promotes both the proliferation and differentiation of preosteoblasts MC3T3-E1 via activation of the MAPK pathway.
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PMID:Exendin-4 promotes proliferation and differentiation of MC3T3-E1 osteoblasts by MAPKs activation. 2664 89

Paget's disease of bone is characterised by overactive osteoclasts that resorb bone at a higher rate than normal. Osteoblasts attempt to repair the damage by laying down new bone which in turn is resorbed leaving a chaotic pattern of lytic and dense sclerotic bone behind. Deformed bone enlarges, becomes vascularised, bends and fractures. No bone is exempt but the skull, pelvis, vertebrae and long bones are commonly affected. Pressure from pagetic bone impinges on the auditory, facial, optic, trigeminal nerves and the spinal cord, risking paraplegia or quadriplegia. Vascular complications include cardiac failure and vertebrobasilar insufficiency. Serum alkaline phosphatase and urine N-telopeptide were used to assess response to treatment with porcine, salmon and human calcitonins, glucagon and bisphonates given alone or in combination. Glucagon has few side effects and controls the disease very rapidly. It can be given alone but because remissions last a few months, repeat courses may be necessary to achieve a long-term permanent quiescent bone state. If complete disease remission is not achieved with the hormone alone, an oral or intravenous bisphosphonate is given at the end of glucagon treatment. Other options are a second-generation bisphosphonate given orally to patients who decline parenteral medication. It remains to be seen whether glucagon affects other bone disorders.
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PMID:Possible role for glucagon in the control of Paget's disease of bone. 3068 79