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 oral administration of dietary chenodeoxycholic acid (1%), but not of ursodeoxycholic acid (1%), to male Sprague Dawley rats results in a significant increase in the colonic adenylate cyclase activity without any influence on the colonic cyclic-AMP phosphodiesterase activity. No effect of chronic bile acid feeding on the response of colonic adenylate cyclase to prostaglandin E2 and vasoactive intestinal peptide is observed. These data emphasize a dependence of the cyclic-AMP adenylate cyclase activation on the chemical structure of the bile acid. This may be of pathophysiologic relevance with respect to the frequently observed diarrhea as a side effect of oral chenodeoxycholic, but not ursodeoxycholic acid therapy for cholesterol gallstone dissolution in man.
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PMID:Different effects of dietary chenodeoxycholic acid and ursodeoxycholic acid on colonic adenylate cyclase in the rat. 298 8

Massive secretory diarrhea is associated with some villous adenomas. The mechanism of this secretion is unknown but the character of the diarrhea resembles that of cyclic nucleotide-mediated diarrheas. We have compared the cyclic nucleotide metabolism of a large secretory villous adenoma with a nonsecretory villous adenoma, a solid carcinoma and their normal mucosae. The adenylate cyclase, cyclic AMP content, and a cyclic AMP-dependent protein kinase ratios in the secretory tumor were increased as compared to these values in the nonsecretory tumors and normal mucosae, a situation similar to that seen with cholera toxin-induced diarrhea. Our data suggest that the massive diarrhea in our patient with a secretory villous adenoma may be related to increased adenylate cyclase activity.
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PMID:Villous adenoma depletion syndrome. Evidence for a cyclic nucleotide-mediated diarrhea. 298 84

5-Hydroxytryptamine (5-HT) has been claimed to mediate intestinal secretion in morphine withdrawal diarrhea through stimulation of local prostaglandin formation without involving cyclic adenosine monophosphate. Therefore, experiments were performed to study (a) the effects of exogenous 5-HT and the cyclic adenosine monophosphate-dependent secretagogue, vasoactive intestinal polypeptide, on intestinal prostaglandin E2 (PGE2) formation and (b) the involvement of calcium in the secretory response to close intraarterial infusion of 5-HT, PGE2, or vasoactive intestinal polypeptide in tied-off loops of rat jejunum in vivo. 5-Hydroxytryptamine and vasoactive intestinal polypeptide reversed fluid absorption to net secretion (p less than 0.01), but only 5-HT caused an increase in luminal PGE2 output (p less than 0.01). Indomethacin and d,l-verapamil prevented only the secretory effect of 5-HT. Exogenous PGE2 (1.6-160 ng/min) reversed absorption to secretion (p less than 0.01) in a dose-dependent manner, irrespective of whether the rats were pretreated with indomethacin or not. Racemic and l-verapamil, but not d-verapamil, markedly reduced (p less than 0.01) the secretory effect of physiologically low doses of PGE2 (1.6 and 16 ng/min), whereas high doses of PGE2 (160 ng/min), which caused a significant increase in mucosal cyclic adenosine monophosphate (p less than 0.005), were not inhibited by verapamil. These data suggest that PGE2 may be an important intermediate in the transduction mechanism leading to 5-HT-induced intestinal secretion, and that physiologic doses of PGE2 may act by facilitating calcium entry, rather than by increasing intracellular calcium through activation of the adenylate cyclase.
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PMID:Significance of calcium for the prostaglandin E2-mediated secretory response to 5-hydroxytryptamine in the small intestine of the rat in vivo. 300 62

Although Plesiomonas shigelloides is considered to cause diarrhea in humans, the mechanisms by which it might do so are not known. Enteric pathogens such as Vibrio cholerae and some strains of Escherichia coli produce enterotoxins that activate adenylate cyclase, increase production of cyclic AMP, and thereby cause elongation of Chinese hamster ovary (CHO) cells in tissue culture. We grew 28 strains of P. shigelloides and the type strain in an iron-depleted medium, and sterile filtrates were examined in CHO cell culture. Filtrates from 24 of the 29 strains produced elongation of CHO cells. These changes could be prevented by heating or by preincubation of the filtrate with cholera antitoxin. These data indicate that P. shigelloides elaborates a cholera-like toxin; such a substance might be important in the pathogenesis of P. shigelloides-associated diarrhea.
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PMID:In vitro production of cholera toxin-like activity by Plesiomonas shigelloides. 365 1

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.
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PMID:[Pharmacological properties of MO-8282, a novel antidepressant]. 379 61

The stimulation of intestinal adenylate cyclase by cholera toxin (CT) was studied in normal and malnourished rats 4 to 24 hr after a 30-min incubation of intestinal loops with the toxin. Whereas in control rats the enzyme activity returned to basal levels after 12 hr of incubation, in malnourished rats the activity of the enzyme remained significantly elevated even after 24 hr of the initial incubation. Malnourished animals had a reduced turnover rate of intestinal cells as determined by thymidine kinase activity. The delayed turnover of intoxicated cells may account for continuous activation of mucosal adenylate cyclase and possibly for prolongation of diarrhea in malnutrition.
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PMID:Stimulation of intestinal adenylate cyclase by cholera toxin in malnourished rats. 393 Oct 85

Vasoactive intestinal peptide (VIP), originally isolated from hog small intestinal mucosa, has been shown to cause small intestinal secretion. More recently, this peptide has been identified in the plasma and tumors of patients with the so-called "pancreatic cholera" syndrome. In order to explore the possible role of VIP in the pathogenesis of this syndrome, we examined the effects of this peptide and other hormones on the cyclic AMP levels, adenylate cyclase activity, and ion transport in in vitro preparations of ileal mucosa. In rabbit ileal mucosa, VIP (20 mug/ml) caused a prompt fivefold increase in cyclic AMP level, whereas nine other hormones, which have been postulated to cause intestinal secretion, failed to exert such an effect. Pentagastrin and glucagon also failed to increase cyclic AMP levels in canine ileal mucosa. An increase in mucosal cyclic AMP levels was observed at a VIP concentration of 0.1 mug/ml and appeared to be nearly maximal at 2.0 mug/ml. VIP (100 mug/ml) stimulated adenylate cyclase activity in a membrane preparation from rabbit ileal mucosa. Secretin (6.0 x 10(-5) M) failed to do so. When added to the serosal side of isolated rabbit ileal mucosa clamped in an Ussing chamber, VIP (2 mug/ml) increased short-circuit current (SCC) and caused net secretion of both Cl and Na. Net Cl secretion exceeded net Na secretion. These effects of VIP on mucosal cyclic AMP metabolism and ion transport are similar to those observed with cholera enterotoxin and certain prostaglandins. VIP was also tested with normal human ileal mucosa. At a concentration of 2 mug/ml it caused a fivefold increase in cyclic AMP level and an increase in SCC of the same magnitude as that caused by 5 mM theophylline. Addition of a second 2-mug/ml dose of VIP and addition of theophylline after VIP produced no further change in SCC. We conclude the VIP stimulates adenylate cyclase and active ion secretion in both rabbit and human ileal mucosa. This may be related to the pathogenesis of diarrhea in patients with the pancreatic cholera syndrome.
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PMID:Vasoactive intestinal peptide stimulation of adenylate cyclase and active electrolyte secretion in intestinal mucosa. 436 34

An Escherichia coli strain isolated from a patient with severe cholera-like diarrhea elaborates a partly heat-labile enterotoxin shown to cause prompt adenyl cyclase stimulation and isotonic fluid secretion by canine jejunum. Both responses disappear upon removal of the enterotoxin. The duration of action of a submaximal dose of this E. coli enterotoxin was brief, despite sustained exposure to the jejunum, suggesting inactivation of the enterotoxin by its interaction with the mucosa. Inoculation of whole bacterial cultures of this E. coli strain into canine duodenum was followed by bacterial survival and induction of net secretion after 4-7 h. The onset of fluid production was associated with increasing gut mucosal adenyl cyclase activity. Washed bacterial cells could also produce fluid secretion. In vivo multiplication of this enterotoxin-producing E. coli was demonstrated 6-12 h after intraduodenal inoculation of approximately 10(6) organisms. This was associated with fluid secretion. Intestinal fluid production occurred without microscopic pathology in the mucosa.
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PMID:Effect of Escherichia coli on fluid transport across canine small bowel. Mechanism and time-course with enterotoxin and whole bacterial cells. 457 57

Purified cholera enterotoxin (20-50 micrograms) and dialyzed cholera filtrate (50-125 mg) increased net glycoprotein synthetic and secretory rates in rat intestinal epithelium. Specific goblet cell mucin secretion was increased 5- to 10-fold. However, other agents that increase intestinal cAMP and accelerate glycoprotein synthesis did not enhance mucin secretion. This was true for dibutyryl cAMP (10(-3) and 10(-2) M) with or without theophylline (10(-3) M) and isoproterenol (10(-4) M) with or without dibutyryl cAMP (10(-3) M). Hyperosmotic mannitol (450 mosmol/l), which increases fluid secretion but does not affect cAMP, and vasoactive intestinal peptide (2 X 10(-7) M), which increases both fluid secretion and cAMP, both failed to increase mucin secretion, implying that fluid "washout" of mucin adherent to the mucosal surface is not responsible for cholera-induced mucin secretion. Cycloheximide, an inhibitor of cholera diarrhea in vivo (20 mg/kg) or in vitro (1 mM), effectively abolished [3H]leucine incorporation into protein but did not affect cholera-induced mucin secretion. Colchicine (10-50 mg/kg) given to block microtubule assembly was similarly without effect on mucin secretion. These findings suggest that there is a dissociation of electrolyte/fluid and mucin secretory processes and cast doubt on the widely accepted notion that all cholera effects are mediated via the well-known adenylate cyclase-cAMP mechanism.
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PMID:Cholera-induced mucin secretion from rat intestine: lack of effect of cAMP, cycloheximide, VIP, and colchicine. 608 74

Antibodies elicited by six synthetic peptides corresponding to various fragments of B subunit of cholera toxin (CT) were evaluated for their cross-reactivity with heat-labile toxin (LT) of Escherichia coli. The antiserum directed towards the peptide CTP3 (residues 50-64) was found highly cross-reactive with the LT, in radioimmunoassay and immunoblotting. This peptide was also the most cross-reactive with intact CT. The antiserum against CTP1 (residues 8-20) was also cross-reactive with the two toxins, although to a much lower extent. Antisera to both CTP1 and CTP3, which are inhibitory towards CT, were found equally effective in neutralizing the biological activity of the E. coli LT. This was manifested by inhibition of both adenylate cyclase activity and fluid secretion into ligated ileal loops of rats. These results might indicate the potential of such synthetic peptides as the basis for a general vaccine against several types of infectious diarrhea.
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PMID:Neutralization of heat-labile toxin of E. coli by antibodies to synthetic peptides derived from the B subunit of cholera toxin. 609 53


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