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 chorontropic response of isolated rabbit atria in normal Tyrode's medium increases monotonically with increasing doses of histamine (9 X 10-7 -9 X 10-4 M). Plots of the inverse of response against the inverse of concentration were linear; and from these plots were derived values fro the theoretical maximum response at 'infinite' dose and for pH histamine concentration required to evoke a half maximum response. Alteration of pH by changing (HCO3-) at a constant pCO2, (Na) and osolality did not appreciably affect the response to histamine in the range pH 7.0-7.6. However, at pH below 7.0 the magnitude of histamine response was reduced at all concentrations of histamine tested. In the pH range 7.0-7.6, additions of NaHCO3 at constant pCO2 increased the spontaneous rate of rabbit atria (in the absence of histamine); however, there was little effect of changing pH (in this range) by altering (HCO3-) at constant pCO2 when (Na+) and osmolaity were kept constant. Immersion in solutions at pH's less than 7.0 led to decline in spontaneous rate and force contraction. It is probable that depression of adenyl cyclase activity rather than a specific change in ionization of histamine receptor is responsible for a decreased response to histamine at pH 6.9.
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PMID:The effect of pH on rabbit atrial response to histamine. 0 37

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

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 phosphaturic effect of parathyroid hormone (PTH), cyclic adenosine monophosphate (cAMP), acetazolamide (Az), and HCO3 loading was studied in normal, thyroparathyroidectomized (TPTX), and Li-treated dogs. PTH administration to normal animals markedly increased fractional excretion (F) of PO4 but had a blunted effect on FPO4 in the Li-treated animals. Cyclic AMP likewise markedly increased FPO4 in the normal animals but had a markedly blunted effect in the Li-treated animals. Az led to a significant increase in FNa, FHCO3, and FPO4 in the normal animals. In the Li-treated dogs, Az induced a significant natriuresis and bicarbonaturia but failed to increase phosphaturia. HCO3 loading in normal dogs caused a significant phosphaturia while having little effect on FPO4 in Li-treated dogs. HCO3 loading to TPTX dogs was associated with a lower FPO4 as compared to normal HCO3-loaded animals. These data suggest that Li administration not only blocks the adenyl cyclase-cAMP system in the renal cortex, but it may also interfere with a step distal to the formation of cAMP, since the phosphaturic effect of both PTH and cAMP was markedly diminished in Li-treated animals.
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PMID:Lithium administration and phosphate excretion. 18 11

The epithelium of the small intestine can both actively absorb and actively secrete electrolytes and water. Secretion can be elicited in vitro by adding cyclic AMP or a stimulator of intestinal mucosal adenylate cyclase (cholera and Escherichia coli enterotoxins, prostaglandins, vasoactive intestinal peptide) or an inhibitor of cyclic AMP phosphodiesterase (theophylline). Cyclic AMP appears to alter intestinal ion transport at two different loci: it inhibits a coupled influx process for Na+ and Cl- at the luminal border, thereby reducing active absorption of NaCl, and it also stimulates the active secretion of anion (or Na+ and anion). A variety of evidence suggests that these two effects of cyclic AMP reside in different types of cells, the former in villus cells and the latter in crypt cells. The latter process is Na+-dependent and is inhibited by low concentrations of ouabain and ethacrynic acid. Active ion absorption in vitro can be enhanced by (1) stimulating Na+-coupled organic solute absorption with glucose, amino acids and possibly also oligo peptides; (2) reducing the HCO3- concentration and/or pH of the serosal bathing solution; and (3) introducing an alpha-adrenergic agonist. Cholera toxin-induced fluid production in vivo can be diminished by the first of these manoeuvres. The in vivo efficacies of the other two have not been evaluated.
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PMID:Regulation of active ion transport in the small intestine. 18 35

To test the hypothesis that lithium is a general inhibitor of hormone-activated adenylate cyclase, we infuse parathyroid hormone (PTH) into human subjects prior to and during lithium carbonate administration. PTH infusion caused a significant increase in urinary cyclic AMP and urinary phosphate excretion. There was no significant difference in these responses in the lithium compared to the control period. In four patients with primary hyperparathyroidism, lithium had no significant effect on serum calcium or phosphate or on tubular reabsorption of phosphate. The data do not substantiate the hypothesis that lithium (at therapeutic concentrations) is a general inhibitor of hormonally-activated adenylate cyclase, nor do they support its potential clinical utility in primary hyperparthyroidism.
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PMID:Lithium does not inhibit the parathyroid hormone-mediated rise in urinary cyclic AMP and phosphate in humans. 18 15

Heart rate rises associated with performance of mental arithmetic tasks were compared in 22 euthymic manic-depressive patients receiving lithium carbonate and 17 drug-free normal controls. The lithium-treated subjects showed a markedly lower heart rate response to the mental arithmetic stimulus. No effect was observed on basal heart rate. The results are consistent with lithium's reported inhibition of noradrenaline-induced rises in adenylate cyclase activity but lack of inhibition of basal adenylate cyclase activity. The biochemical and psychophysiological findings may parallel lithium's unique ability to calm excited behavior without sedating normal behavior.
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PMID:A possible cardiovascular effect of lithium. 21 67

Renal phosphorus handling was evaluated in 12 lithium carbonate-treated psychiatric patients. Serum phosphorus was normal and serum lithium values were within the therapeutic range in all subjects. Serum calcium concentrations measured in 6 of the patients were found to be within the normal range; in the same patients serum parathyroid hormone levels were normal in 4 and slightly elevated in 2. Phosphorus clearance (14 +/- 3 [se] ml/min) and tubular reabsorption of phosphorus (88 +/- 2%) during oral sodium bicarbonate loading were not significantly different from those in 10 healthy control subjects. In a subgroup of 5 patients and 5 control subjects, phosphorus excretion did not increase after bicarbonate loading. In these subjects, phosphorus excretion rates after bicarbonate loading were not different. Although experimental studies suggest that lithium inhibits renal cortical adenylate cyclase stimulation by parathyroid hormone, our data did not indicate any striking effect of long-term lithium administration on serum calcium and serum phosphorus or on renal phosphorus handling.
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PMID:Effect of long-term lithium administration on renal phosphorus handling. 84 75

Recently, several lines of evidence have indicated the important roles of glial cells, especially astrocytes, in the regulation of neuronal functions. The neuron-glia interaction is one of the most important issues in neuroscience, including neuropharmacology. I reviewed the present status and perspectives on the physiologic and pathologic functions of astrocytes in relation to the roles of intracellular Cl-. Astrocytes have different types of Cl- transport systems, such as voltage-sensitive and ligand-gated channels; HCO3(-)-Cl- exchange; and Na+, K+, Cl- cotransport systems. Anion exchange and cotransport systems are responsible for intracellular pH regulation and astrocytic volume regulation, respectively. Especially, astrocytic volume regulation is physiologically important for reducing the concentrations of K+ and glutamate in the extracellular space by their uptake systems. Disturbance of astrocytic volume regulation is expressed as astrocytic swelling, which is usually observed in various brain pathologic states including ischemia. Experimentally, glutamate caused a typical swelling of astrocytes in culture by Cl- and Ca(++)-dependent processes. Glutamate-induced swelling is qualitatively different from reversible swelling induced by hypoosmotic medium. Recently, we found that Cl- is intracellular factor for modulating the receptor-adenylate cyclase system in brain slices. Similarly, the receptor- and forskolin-stimulated adenylate cyclase of astrocytes showed a clear Cl- dependence. This was functionally confirmed by astrocytic morphological transformation induced by the cyclic AMP system.
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PMID:[Regulation by chloride ion of astroglial cell functions and morphological transformation]. 131 34

The mechanisms of action of lithium and antidepressants were investigated with reference to effects of these drugs on monoaminergic receptors and receptor-coupled adenylate cyclase systems in rat brain. Oral administration of lithium carbonate for 21 days decreased significantly the density of beta-adrenergic receptors in rat cerebral cortex, which is the same change as reported as the result of long-term treatment with many antidepressants. With regard to 5-hydroxytryptamine (5-HT) receptor subtypes, lithium treatment reduced the maximum number of 5-HT1A receptors in rat hippocampus but not in cerebral cortex, whereas repetitive injections with imipramine or desipramine did not. beta-Adrenoceptor-coupled adenylate cyclase activity was subsensitized by long-term lithium treatment in consistency with above-mentioned down-regulation of beta-adrenergic receptors. Stimulation of adenylate cyclase activity by non-hydrolyzable GTP analogue, guanyl-5'-ylimidodiphosphate (Gpp(NH)p), was, however, unaltered in lithium-treated rats as compared with controls. On the other hand, 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase in rat hippocampal membranes was not altered by chronic treatment with lithium or antidepressants. Gpp(NH)p-induced inhibition of forskolin-stimulated adenylate cyclase activity was not influenced by lithium treatment, either. [3H]Forskolin binding to rat cerebral cortex, which is assumed to be associated with the activated complex of catalytic subunit of adenylate cyclase and stimulatory guanine nucleotide-binding regulatory proteins (Gs), was not changed by administration of lithium or antidepressants under any condition studied. Pertussis toxin (islet-activating protein, IAP) sensitive G proteins (Gi/Go) as determined by using IAP-catalyzed [32P]ADP-ribosylation was not altered by lithium- or antidepressant-treatment, either. The implication of these results is discussed with a view of clarifying the mechanisms of action of these thymoleptic drugs.
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PMID:[Effects of lithium and antidepressants on monoaminergic receptors and receptor-coupled adenylate cyclase system in rat brain]. 131 19


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