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 purpose of this study was to evaluate the coupled beta-adrenergic receptor (BAR) and adenylate cyclase (AC) system of the lung during the course of the bleomycin-(Bleo) induced pulmonary fibrosis in hamsters. The BAR population, dissociation constants (Kd), AC activity, and its sensitivity to various stimulators were studied at 2, 4, 7, 14, and 21 days after intratracheal administration of either 1 unit of Bleo or an equivalent volume of saline. The BAR population in the lungs of Bleo-treated animals did not differ from control at the early times, but it was significantly reduced to 5.9 X 10(3) fmol and 3.6 X 10(3) fmol from the control values of 1.1 X 10(4) fmol and 1.5 X 10(4) fmol per lung at 14 and 21 days after treatment, respectively. The Kd values for control hamster lung ranged from 2.5 X 10(-11) M to 3.7 X 10(-11) M, and for Bleo-treated hamster lung, from 2.7 X 10(-11) M to 4.8 X 10(-11) M. The Kd at the earliest time, 2 days after treatment, did not differ significantly from the Kd values at the subsequent times in control, while for Bleo-treated hamster lung, the Kd values at 7, 14, and 21 days were significantly higher than the Kd at 2 days after treatment. The Kd values for Bleo-treated hamster lung were also significantly higher than control at 14 and 21 days. The AC activity of the lung in Bleo-treated hamster was significantly reduced to 67%, 40%, 38%, and 50% of their respective controls in response to H2O (basal), GTP (10(-4) M), GTP + isoproterenol (10(-4) M each), and NaF (10 mM) at 21 days after treatment. The extent of AC stimulation in Bleo-treated hamster lung in response to various stimulators was generally less than that of saline control. Reductions in the BAR population and increased Kd values in Bleo-treated hamster lung were attributed to its fibrogenic ability and not to nutritional deficiency, which may partly be accountable for decreased AC activity of the lung in these animals. However, there were qualitative differences in the lung AC activity between Bleo-treated and nutritionally deprived hamsters, since the enzyme from the latter group was generally more responsive to stimulators than the enzyme from the former group. It was concluded from the findings of this study that an impairment in the coupled BAR and AC system of the lung may be partly responsible for the fibrogenic ability of bleomycin.
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PMID:Impairment in coupled beta-adrenergic receptor and adenylate cyclase system during bleomycin-induced lung fibrosis in hamsters. 245 79

The possibility that an increased intracellular concentration of cyclic AMP (cAMP) can regulate the extent of muscarinic receptor-stimulated phosphoinositide (PPI) turnover in the human neuroblastoma cell line SK-N-SH was examined. Addition of either forskolin (or its water-soluble analog, L-85,8051), theophylline, isobutylmethylxanthine, or cholera toxin, agents that interact with either the catalytic unit of adenylate cyclase, cAMP phosphodiesterase, or the guanine nucleotide binding protein linked to adenylate cyclase activation, resulted in a 45-181% increase in cAMP concentration and a 27-70% inhibition of carbachol-stimulated inositol phosphate release. Through the use of digitonin-permeabilized cells, the site of inhibition was localized to a step at, or distal to, the guanine nucleotide binding protein that regulates phospholipase C activity. In contrast, when intact SK-N-SH cells were exposed to prostaglandin E1, the ensuing increases in cAMP were not accompanied by an inhibition of stimulated PPI turnover. These differential effects of increased cAMP concentrations on stimulated PPI turnover may reflect the compartmentation of cAMP within SK-N-SH cells.
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PMID:Muscarinic receptor-stimulated phosphoinositide turnover in human SK-N-SH neuroblastoma cells: differential inhibition by agents that elevate cyclic AMP. 247 99

Monensin, a highly selective sodium ionophore, inhibits vasopressin-stimulated water flow in toad urinary bladder pretreated with naproxen, an inhibitor of prostaglandin synthesis. Inhibition is partially dependent on the presence of sodium in the serosal medium, but not on serosal calcium. We have found that monensin does not inhibit water flow generated by forskolin, cyclic AMP, or isobutyl methyl xanthine (MIX); indeed, an enhancement of water flow was seen following cAMP and MIX, as well as following 0.2 microM forskolin. Our findings suggest that monensin uncouples the vasopressin-receptor-G protein-adenylate cyclase sequence at some early step, by a mechanism that remains unknown, but that may directly or indirectly involve intracellular sodium.
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PMID:Evidence that monensin inhibits vasopressin-stimulated water flow at an early step in the receptor-adenylate cyclase sequence. 247 41

Vanadate has been used in many cellular systems to elucidate mechanisms of enzyme action. Vanadate inhibits Na-K adenosine triphosphatase (ATPase) activity in many tissues. In isolated collecting tubule it inhibits sodium transport and vasopressin-stimulated water flux, the latter presumably distal to cyclic AMP formation. Depending upon the tissue studied, vanadate also stimulates a variety of cellular reactions including adenylate cyclase, glucose oxidation and glycogen synthesis. We studied the effect of varying concentrations of vanadate on N-ethylmaleimide (NEM)-sensitive ATPase activity in microdissected segments of rat nephron. In proximal convoluted tubule and in cortical, medullary and papillary collecting ducts vanadate had no effect on enzyme activity. In medullary and cortical thick ascending limbs, however, vanadate significantly stimulated NEM-sensitive ATPase activity (medullary thick ascending limb, 241 +/- 14 pmol/mm/hr vs. 531 +/- 74 pmol/mm/hr; control vs. (1 mM) vanadate, respectively; n = 14, P less than 0.01). The stimulatory effect of vanadate on NEM-sensitive ATPase activity was present at 5 microM vanadate, a concentration that inhibited Na-K ATPase activity approximately 80%. Metabolic acidosis also stimulated enzyme activity in the thick ascending limb, and the effect of vanadate was not additive. Metabolic alkalosis had no effect on NEM-sensitive ATPase in the thick ascending limb, but the stimulatory effect of vanadate was still seen. These data document that the NEM-sensitive ATPase in thick ascending limb is different from that found in other nonmammalian proton secretory epithelia which are vanadate inhibitable. The results with vanadate plus metabolic acidosis suggest that both are acting via the same mechanism.
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PMID:Vanadate stimulates the N-ethylmaleimide-sensitive adenosine triphosphatase in rat nephron. 252 98

Toad urinary bladder epithelial cells grown in culture (primary) show a significant increase in water-soluble inositol phosphates when treated with 10(-8) M vasopressin (AVP), but not with (1-deamino-8-D-arginine)vasopressin (dDAVP), a V2-agonist. The increase in inositol phosphates was blocked by the V1-antagonist, d(CH2)5Tyr(Me)AVP, suggesting a V1-coupled phosphoinositide breakdown. The V1-antagonist had no effect on basal adenylate cyclase activity nor on that stimulated by AVP. However, the V1-antagonist was found to attenuate the hydrosmotic response of AVP, suggesting some role of the V1-receptor cascade in the water flow response. Mezerein (MZ), a non-phorbol activator of protein kinase C (PKC) increased osmotic water flow when added to the mucosal surface. The response was less in magnitude and occurred over a longer period (90 min) than that observed with AVP. In an attempt to emulate the V1-response, activation of PKC, and an increase in intracellular calcium, toad bladders were incubated with MZ and the calcium ionophore A23187 (IP). It was found that IP enhanced the water flow response to MZ at all times measured. Mz and IP were also found to enhance cAMP-mediated water flow, suggesting that apical membrane permeability may be regulated in part through V1-receptor stimulation and its respective second messengers. Collectively, these observations suggest that the V1 receptor may play a role not only as part of a negative feedback system, but also as an integral component of the enhanced water permeability that occurs at the apical membrane.
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PMID:Contribution of the vasopressin V1 receptor to its hydrosmotic response. 252 41

Previous studies suggest that circulating levels of vasopressin (AVP) influence the responsiveness of the kidney to AVP. To determine how changes in renal AVP receptors and adenylate cyclase (AC) contribute to such altered responsiveness, we analyzed AVP receptors and AVP-sensitive AC in kidneys from Sprague-Dawley, Long-Evans and homozygous Brattleboro rats. In autoradiographic studies, the distribution of [3H]AVP binding sites was similar in all groups, corresponding to the location of AVP-sensitive AC: collecting ducts greater than outer medullary collecting ducts greater than medullary thick ascending limb greater than cortical collecting ducts. No differences in AVP receptor affinity or content were observed in kidney medullary membranes from Sprague-Dawley, Long-Evans or Brattleboro rats (KD = 0.8, 0.9, and 0.7 nM; Bmax = 116 +/- 9, 95 +/- 11 and 98 +/- 6 fmol/mg). Basal and AVP-stimulated AC activities were lower in kidney membranes from Brattleboro rats compared with Sprague-Dawley and Long-Evans animals (basal = 28 +/- 4, 40 +/- 4 and 38 +/- 3 pmol cAMP/mg/min; EDmax = 57 +/- 5, 80 +/- 7 and 71 +/- 2 pmol cAMP/mg/min) with no change in ED50. In 48-hour water-deprived Sprague-Dawley rats, AVP receptors were decreased from 116 +/- 9 to 58 +/- 2 fmol/mg, suggesting that AVP receptors are down-regulated by elevated AVP blood levels. The absence of changes in basal or AVP-stimulated AC in dehydrated rats indicates that receptor-AC coupling is normal and that maximum AC activation can occur with partial receptor occupancy. The data also indicate that impaired renal responsiveness to AVP in Brattleboro rats is not due to down-regulation of AVP receptors.
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PMID:Physiologic regulation and distribution of the renal vasopressin receptor. 253 25

The vasopressin antidiuretic (V2) antagonist activity of the position 6 stereoisomers of four vasopressin analogs were tested for water diuretic activity in the rhesus monkey and for activity to inhibit vasopressin-stimulated adenylate cyclase activity in rhesus monkey and human renomedullary tissue in vitro. Replacement of the mercapto groups of the cysteine residues with methylene groups resulted in compounds having similar in vitro potencies to their disulfide analogs; however, these 'dicarba' compounds demonstrated more potent aquaretic activity. Position 6 D enantiomers were associated with less vasopressin antagonist activity in vitro in both species. Based upon these studies, the most potent aquaretic structure identified was the dicarba analog SK & F 105494.
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PMID:Vasopressin receptor antagonism in rhesus monkey and man: stereochemical requirements. 254 Sep 87

The triggering action of physiological saline in the miracidial transformation of Schistosoma mansoni was analyzed using various agents affecting cAMP- and Ca2+-dependent pathways. Potent activators of adenylate cyclase, such as forskolin and serotonin, strongly inhibited the transformation provoked by saline in RPMI-1640. These inhibitory actions were diminished by the combined administration of phosphodiesterase activators such as ammonium salts or imidazole. Furthermore, the exposure of miracidia to ammonium salts or imidazole in dechlorinated tap water "mimicked" the transformation, i.e., the cessation, of swimming and then shedding of epithelial plates. This mimic transformation was also inhibited by serotonin or forskolin. In contrast, treatment of miracidia with Ca2+ antagonists such as TMB-8 (an inhibitor of Ca2+ release), nicardipine (a Ca2+ channel blocker), or W-7 (a calmodulin inhibitor) in tap water produced severe vesiculation on their body surfaces and resulted in death. However, these toxic effects were abolished by a combined administration of these Ca2+ antagonists with saline or NH4Cl, and the transformation was reestablished except with W-7 treatment. W-7 strongly inhibited the triggering action of saline and NH4Cl and the worms swam slowly, whereas W-5, an inactive analogue of W-7, had no inhibitory effect on the transformation. These results suggest that the initiation of micracidial transformation to young sporocysts may be synergistically regulated by cAMP and Ca2+ and that a decrease in cAMP levels and an increase in Ca2+ mobilization may be provoked in worms transformed by saline, ammonium salts, or imidazole.
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PMID:Possible roles of cAMP and Ca2+ in the regulation of miracidial transformation in Schistosoma mansoni. 254 28

Ethanol prevents the decrease of the number of beta-adrenoceptors in the cerebral cortex induced by chronic treatment of rats with desipramine. The activation of the adenylate cyclase, the second messenger, by beta-adrenergic agonists is reduced somewhat less than after treatment with desipramine alone. The present paper examined the hypothesis that ethanol inhibits the neuronal adaptation to desipramine chronic treatment at the functional level as well. Desipramine reduced exploratory behavior (crossings, rearings) as did ethanol. Combined treatment attenuated the effect of desipramine. Cognitive performance was investigated using an active avoidance paradigm. Desipramine-treated rats did not learn the task in contrast to control animals. Again, combination treatment with ethanol improved the ability of the rats to perform the task. The activity of cerebral beta-adrenergic mechanisms was assessed by injection of salbutamol, a beta-adrenoceptor agonist in rats pretreated with 5-hydroxytryptophan (5-HTP). The augmentation of the 5-HTP-induced wet dog shake behavior by salbutamol was observed in all animals independent of the chronic treatment. However, rats treated with desipramine were less active than those treated with tap water or ethanol. The effect of desipramine in the presence of a high concentration of salbutamol was attenuated by ethanol. The observed increase of the number of wet dog shakes correlates with the function of these receptors. In two paradigms, spontaneous motility and apomorphine-induced hypothermia, ethanol did not affect the action of desipramine. It is noteworthy that desipramine acted in both situations within a short time period (minutes to hours). The findings strongly suggest that ethanol can prevent adaptive changes in the brain induced by chronic treatment with the antidepressant desipramine. This is of special interest since the adaptation of beta-adrenoceptors is thought to be critical for the antidepressant efficacy of various therapeutic interventions applied in psychiatric practice.
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PMID:Effects of desipramine on rat behavior are prevented by concomitant treatment with ethanol. 254 96

Cholera toxin acts in vivo by activating intestinal adenylate cyclase. This study was designed to determine (1) whether normal rat epithelial intestinal cell lines (IRD 98 and IEC 17) respond to cholera toxin (CT) by an increased concentration of cyclic AMP and (2) whether the yeast Saccharomyces boulardii, which reduced CT-induced secretion of water and electrolytes using the isolated jejunal loop technique, has an effect on these models. The cAMP concentration evaluated in cells exposed to Saccharomyces boulardii and to cholera toxin (1 microgram/ml for 90 min) was compared to the concentration of cAMP obtained in control cells without yeast. Prior exposure of IRD 98 and IEC 17 cells to Saccharomyces boulardii, reduced CT-induced cAMP by 50 p. 100. This effect disappeared after destruction of the yeast by heating. Results show that the IRD 98 and IEC 17 cells are good models for in vitro investigation of the effects of cholera toxin. Our results suggests that Saccharomyces boulardii prevents the water and electrolyte secretion induced by cholera toxin.
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PMID:[Response to cholera toxin of 2 epithelial intestinal cell lines. Effect of Saccharomyces boulardii]. 254 74


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