Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of various adenosine phosphate compounds, theophylline, histamine,a nd metiamide, on steady rates of acid secretion by isolated fundic mucosa of the rabbit were measured by the pH stat method. Cyclic adenosine 3':5'-monophosphate (cyclic AMP), N(6), O(2')-dibutyryl adenosine 3':5'-monophosphate and theophylline increased the rate of acid secretion. Addition of theophylline in a concentration which has no stimulatory effect, reduces the effective concentrations cyclic AMP or histamine required for stimulation of acid secretion. Measurements of lactate, pyruvate, and CO2 appearances indicated that the increases in acid secretory rates were predominantly due to H+ and not organic acid accumulation in the luminal bath-secretion. Metiamide prevented the stimulatory effects of histamine and ATP. However, metiamide did not prevent the stimulatory effects of N(6),9(2')-dibutyryl adenosine 3':5'-monophosphate, theophylline, or 5'-AMP. The results provide further evidence for a role of cyclic AMP in governing the rate of acid secretion by rabbit stomach. The data also are consistent with histamine and ATP (at least in the concentration used) requiring adenylate cyclase activity for stimulation of acid secretion and 5'-AMP inhibiting phosphodiesterase activity.
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PMID:Effects of cyclic adenosine 3':5'-monophosphate and related agents on acid secretion by isolated rabbit gastric mucosa. 16 24

1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(-6)M, when micro-injected, causes a sharp rise in the radio-Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre-injecting 100 or 500 mM-EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre-injecting the protein inhibitor of Walsh and practically abolished by pre-injecting 500 mM-EGTA and soaking in Ca-free artificial sea water, ASW. 5. The Ca2+-independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+-free, Li+-ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain-insensitive Na efflux into HEPES-Ca2+-free ASW at pH 6-3. These same fibres show a marked response to cAMP. (II) The ouabain-insensitive Na efflux into HCO3-, Ca2+-free ASW from fibres pre-treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2-sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain-insensitive Na efflux into HCO-3, Ca2+-free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP-dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon.
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PMID:Mode of stimulation by adenosine 3':5'-cyclic monophosphate of the sodium efflux in barnacle muscle fibres. 18 61

The lower O2 tension and more active anerobic metabolism that pertain in the inner medulla (IM) of kidney relative to cortex (C) are well recognized, but there is no evidence that O2 availability constitutes a limiting or regulatory factor in IM metabolism or function. In the present in vitro study, we examined the effects of O2 on adenosine 3',5'-monophosphate (cAMP) metabolism in slices of rat renal C and IM. After a 20-min incubation of slices in Krebs Ringer bicarbonate buffer with 95% O2 + 5% CO2 serving as the gas phase, the cAMP content of IM was 6-10 fold higher than that of C in either the presence or absence of 2 mM 1-methyl-3-isobutylxanthine in the incubation media. In slices of IM incubated for 20 min with 1-methyl-3-isobutylxanthine, cAMP was 22.5+/-SE 2.48 pmol/mg wet weight at 95% O2 and 4.37 without O2. Oxygenation of O2-deprived IM increased cAMP twofold in 2 min, an effect fully expressed in 5 min (fivefold increase). Further, cAMP of IM rose progressively and significantly over a range of atmospheric O2 content from 0 to 50% conditions which should reproduce and encompass O2 tensions that pertain in tissues in vivo. By contrast, basal cAMP content of C varied less than twofold in the presence of 95% versus no O2, implying that O2 modulation of cAMP was specific for IM. Indomethacin and meclofenamate, structurally distinct inhibitors of prostaglandin synthesis, both significantly decreased basal cAMP accumulation in oxygenated slices of IM but not of C. Meclofenamate also reduced basal adenylate cyclase activity determined in homogenates prepared from slices of IM which had been incubated at 95% O2. In slices of IM previously exposed to indomethacin or meclofenamate at 95% O2, a maximally effective concentration of exogenous prostaglandin E1 restored cAMP and adenylate cyclase activity to levels which approximated those observed at 95% O2 in the absence of an inhibitor of prostaglandin synthesis. These results suggest that O2 enhancement of cAMP content in IM may be mediated at least in part by local prostaglandins.
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PMID:Modulation of the cyclic AMP content of rat renal inner medulla by oxygen: possible role of local prostaglandins. 18 90

Murine 3T3-L1 fibroblasts enter a differentiation program subsequent to prolonged maintenance in the confluent state and develop into adipocytes. The hormone sensitivity of adenylate cyclase and the physiological responsiveness to insulin were compared in 3T3-L1 preadipocytes and adipocytes. The following observations, comprising several distinct categories of hormone responsiveness, were made. (a) (2.5 micronM) isoproterenol stimulated adenylate cyclase 15-fold in adipocyte homogenates, but only 2.5-fold in preadipocyte preparations, suggesting a considerable magnification in beta-adrenergic responsiveness during development. (b) A totally new control element, adrenocorticotropic hormone responsiveness, was incorporated into the adenylate cyclase system of the adipocytes. (c) Sensitivity to prostaglandin E1 was observed in both preadipocytes and adipocytes, but no change in responsiveness could be detected in the differentiated cells. (d) Glucagon-sensitive adenylate cyclase could not be detected in either preadipocytes or adipocytes. (e) Both preadipocytes and adipocytes possess considerable insulin binding activity, but near physiological levels of insulin stimulate the conversion of glucose to CO2 and lipid only in the differentiated cells.
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PMID:Acquisition of increased hormone sensitivity during in vitro adipocyte development. 19 37

The present experiment was planned to verify the effect of calcium on adenyl cyclase in isolated human adrenal cells. Normal adrenal glands were obtained surgically from patients with primary aldosteronism and advanced breast cancer. Isolated adrenal cells were prepared by the modified Haning's method. They were incubated at 37C under a gas mixture of 95 percent O2: 5 percent CO2 in calcium-free Krebs-Ringer bicarbonate buffer solution containing 0.2 percent glucose and 0.5 percent fatty acid-free bovine serum albumin, to which various doses of CaCl2 or ACTH were added. Thirty minutes later, cyclic-AMP was measured by cyclic-AMP assay kit (The Radio-chemical Center, Amersham). 11-OHCS was estimated fluorometrically by the modified Silber's method after incubation for 2 hours. In the calcium-free incubation medium, productions of 11-OHCS and cyclic-AMP were negligible. In the concentration of 2.54 mM/L of calcium, 11-OHCS production increased with significant difference statistically, while the increase of cyclic-AMP production was not significant. In the concentration of 12.70 mM/L of calcium, however, cyclic-AMP production increased remarkably. When ACTH was added to the incubation medium containing 2.54 mM/L of calcium, productions of 11-OHCS and cyclic-AMP also increased remarkably. These results indicate that adenyl cyclase of human adrenocortical cells is directly stimulated by calcium and suggest that calcium acts as the second messenger of ACTH.
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PMID:[The effect of calcium on steroidogenesis in isolated human adrenal cells (author's transl)]. 20 11

Using tunicamycin, we have investigated the role of glycoproteins in membrane transport. Tunicamycin is a glucosamine-containing antibiotic that specifically inhibits dolichol pyrophosphate-mediated glycosylation of asparaginyl residues of glycoproteins. Inhibition of protein glycosylation in chick embryo fibroblasts by tunicamycin or other inhibitors of glycosylation resulted in defective transport of glucose, uridine, and amino acid analogs (alpha-aminoisobutyrate and cycloleucine). The defect in glucose transport is accompanied by decreased glucose metabolism, as determined by rates of CO2 and lactate production. In contrast, tunicamycin treatment did not affect other membrane-associated processes, such as secretion of fibronectin and procollagen, uptake of glucose by passive diffusion, Na+/K+ ATPase and adenylate cyclase activities, or stimulation of adenylate cyclase by prostaglandin and cholera toxin. Two glucose/glycosylation-regulated membrane proteins with apparent subunit molecular weights of 95,000 and 75,000 were induced by tunicamycin treatment. Our results indicate that glycoprotein glycosylation is required for membrane transport.
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PMID:Evidence for role of glycoprotein carbohydrates in membrane transport: specific inhibition by tunicamycin. 21 20

The catecholamines, adrenaline and noradrenaline, are released into the circulation of fish during a variety of physical and environmental disturbances that share the common feature of a requirement for enhanced blood oxygen transport. Indeed, the dominant factor controlling the mobilization of catecholamines from chromaffin tissue is a depression of blood oxygen content usually coinciding with a reduction of hemoglobin-O2 (Hb-O2) binding to 50-60% saturation. The elevation of plasma catecholamine levels, under such conditions, activates a beta-adrenergic cyclic AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness AMP-dependent Na+/H+ exchanger on the red blood cell (rbc) membrane. The adrenergic responsiveness of the rbc Na+/H+ exchanger to catecholamines varies both within and between species. Such inter- and intra-specific differences may reflect, in part, the availability of cell surface beta-adrenoceptors that are functionally coupled to adenylate cyclase. The activation of rbc Na+/H+ exchange and the accompanying profound adjustments of intracellular and extracellular acid-base status, nucleoside triphosphate (NTP) levels, and cooperativity of Hb-O2 binding have important consequences on both O2 and CO2 transfer and transport in the blood that vary markedly at the sites of oxygenation (the gill) and deoxygenation (the tissues) thereby enabling simultaneous amelioration of O2 loading and unloading. At the gill, oxygen transfer is enhanced owing to increases in Hb-O2 affinity and capacity while at the tissues, oxygen delivery is facilitated by a reduction of Hb-O2 affinity. This reduction in affinity at the tissues is a consequence of the combined effects of increased cooperativity of Hb-O2 binding and a rise in venous PCO2 (PvCO2) caused by the titration of HCO3- by H+ extruded by the rbc Na+/H+ exchanger. This elevation of PvCO2 may contribute to the rise in arterial PCO2 (PaCO2) observed after adrenergic activation of rbc Na+/H+ exchange that is caused primarily by impairment of rbc CO2 excretion related to modification of the intracellular acid-base status.
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PMID:Control and consequences of adrenergic activation of red blood cell Na+/H+ exchange on blood oxygen and carbon dioxide transport in fish. 132 42

In order to investigate the effects of prostaglandin E1 (PGE1) used in hypotensive anesthesia on the adrenal endocrine function, aldosterone, corticosterone (Comp B) and cAMP production were measured in isolated glomerulosa (G-c) and fasciculata cells (F-c) of the rats. Rat glomerulosa and fasciculata cells were obtained by enzymatic digestion of the adrenals of male wistar rats. The cell pellet was suspended in Hank's balanced salt solution containing 0.1% BSA and distributed in 900 microliters aliquots to polyethylene tubes. The samples were preincubated for 90 min in a 37 degrees C water bath aerated with 5% CO2/95% O2. PGE1 or ACTH 50 microliters was added and incubated for 4 hr. Total volume of the incubation medium is 1.0 ml. Aldosterone and cAMP were measured by radioimmunoassay and Comp B was determined by fluorimetric method. PGE1 increased significantly the basal secretion of aldosterone and Comp B in G-c and F-c, respectively. The steroidogenic effect of PGE1 was dose dependent in aldosterone production. This aldosterone production was also accompanied with cAMP production. On the other hand, significant increase of cAMP was not observed in comp B production. These results suggest that cAMP may be the second messenger in PGE1-induced aldosterone production in G-c. But PGE1 receptors in F-c seem not to be coupled to the adenylate cyclase system. The addition of ACTH and PGE1 resulted in inhibition of aldosterone secretion when compared with that obtained by ACTH alone. Several researchers have shown that low doses of PGE1 depressed the basal aldosterone secretion. These findings may be contributing to Na-uresis effect during PGE1-induced hypotension.
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PMID:[Role of prostaglandin E1 in steroidogenesis by isolated rat adrenal cells]. 166 72

We found that anion channel blockers such as phosphotungstate and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) enhanced HCO3(-)-induced activation on porcine epididymal sperm. In the presence of these compounds, HCO3- increased the motility, respiration rate and especially the cAMP content of the sperm to a greater extent than did HCO3- alone. The enhancing effects were not observed in the absence of HCO3-, but were evident when the concentration of HCO3- was low. These compounds did not significantly alter the intracellular pH and did inhibit the adenylate cyclase activity of the sperm plasma membrane. When these compounds were added to sperm homogenate with ATP, the cAMP formed was reduced compared to the control. In addition, these compounds inhibited both the SO4(2-) influx and efflux of the sperm. From these results, we conclude that the anion channel blockers tested principally inhibit the efflux of endogenous HCO3- derived from metabolic CO2, so that HCO3- accumulates intracellularly and stimulates the adenylate cyclase of the sperm.
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PMID:The enhancing effects of anion channel blockers on sperm activation by bicarbonate. 169 90

The effect of interference with diacylglycerol metabolism was investigated in pancreatic mouse islets. In the presence of the diacylglycerol lipase inhibitor RHC 80,267, glucose-induced insulin secretion was reduced 50-60%; whereas carbacholin-induced insulin secretion was unaffected. Addition of the diacylglycerol kinase inhibitor R 59,022 did not change glucose-stimulated insulin secretion but abolished the inhibition seen in the presence of RHC 80,267. RHC 80,267 increased islet glucose utilisation, measured as formation of tritiated water from 5-[3H]-glucose, 3-fold but did not affect glucose oxidation to CO2, lactate production or islet ATP levels. Glucose utilisation in leucocytes and hepatocytes was not increased by addition of RHC 80,267. Islet lipid production from glucose was augmented 4-fold in the presence of RHC 80,267 but only accounted for about 5% of the increase in glucose utilisation. The activity of adenylate cyclase and phosphoinositide-specific phospholipase C was unaffected by RHC 80,267. Concentrations of RHC 80,267 below 35 mumol/l did not alter the activity of phospholipase A2; whereas higher concentrations of the drug inhibited phospholipase A2 activity approx 25%. The data support the hypothesis that production of arachidonic acid from diacylglycerol may be involved in regulation of insulin secretion.
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PMID:Effect of diacylglycerol lipase inhibitor RHC 80267 on pancreatic mouse islet metabolism and insulin secretion. 265 50


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