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Biomedical subjects

E Beubler

Publications and source records attributed to E Beubler.

At least 37 records · Page 2Linked to original sources
PubMed1993

Antisecretory activities of orally administered loperamide and loperamide oxide on intestinal secretion in rats.

In-vivo experiments in the rat jejunum have been performed to compare the antisecretory effect of orally administered loperamide with the effect of its pro-drug, loperamide oxide. Both loperamide and loperamide oxide, administered orally, reduced the secretory effect of prostaglandin E2 (32 ng min-1, intra-arterially) in the jejunum and the colon. Differences between the two drugs as to time course and dose response can be seen. Loperamide oxide shows its antisecretory effect in the jejunum, and at a dose of 2 mg kg-1 also shows its effect in the colon 1 h after administration. The effect was maximal after 2 h and decreased after 4 h. A dose-response relationship was demonstrated at 2 h in the jejunum and the colon. In comparison, the effect of loperamide started later, and a good dose-response relationship was not observed in the jejunum or in the colon, higher doses always appearing less effective than lower doses.

Administration, Oral↗
PubMed1993

Serotonin antagonists inhibit sennoside-induced fluid secretion and diarrhea.

The aim of this study was to investigate whether 5-hydroxytryptamine (serotonin, 5-HT) is involved in the mediation of sennoside-induced colonic fluid secretion and diarrhea. Oral administration of purified sennosides (25, 40 and 64 mg/kg) dose-dependently reversed net fluid absorption to net fluid secretion, enhanced the incidence of diarrhea and stimulated the release of 5-HT into the colonic lumen from 7.1 to 17.3 ng/g wet weight. The 5-HT2 antagonist ketanserin and the 5-HT3 antagonist tropisetron dose-dependently but only partially reduced sennoside (40 mg/kg)-induced fluid secretion whereas the 5-HT3 antagonist granisetron dose-dependently reduced and at 300 micrograms/kg totally abolished sennoside-induced secretion. Granisetron, but not ketanserin and tropisetron, reduced the incidence of diarrhea in sennoside-treated rats, indicating the involvement of 5-HT also in acceleration of large intestinal transit. It is concluded that 5-HT is an important mediator both of sennoside-induced fluid secretion in the rat colon and of diarrhea.

Animals↗
PubMed1992

5-HT receptor antagonists and heat-stable Escherichia coli enterotoxin-induced effects in the rat.

The effect of heat-stable E. coli enterotoxin on intestinal fluid secretion is commonly considered to be mediated by stimulation of mucosal cyclic guanosine monophosphate (cGMP). It was demonstrated recently that 5-hydroxytryptamine (5-HT) acts as an important mediator in cholera toxin-induced fluid secretion. To elucidate the possible involvement of 5-HT in the secretory response to heat-stable E. coli enterotoxin, in vivo experiments were performed in the rat jejunum. The inhibitory effects of the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist tropisetron and indomethacin were studied in heat-stable E. coli enterotoxin-induced fluid secretion. Tropisetron and ketanserin (100 micrograms/kg each) alone only partially reduced the secretory effect of the toxin. However, in combination, the two blockers (100 plus 100 micrograms/kg) significantly reduced and at 200 plus 200 micrograms/kg totally abolished heat-stable E. coli enterotoxin-induced secretion without influencing the enterotoxin-induced increase in cGMP. Pretreatment with indomethacin (10 mg/kg) reduced the secretory response to the enterotoxin by about 50%. These results support the concept that 5-HT is an important mediator in intestinal fluid secretion induced by heat-stable E. coli enterotoxin. The enterotoxin may use 5-HT to stimulate prostaglandin formation via 5-HT2 receptors and to activate neuronal structures via 5-HT3 receptors.

Animals↗
PubMed1992

Effect of cholera toxin on the human jejunum.

In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.

Adult↗
PubMed1990

Protein kinase C and intestinal fluid secretion: involvement of prostaglandin E2 but not of 5-hydroxytryptamine.

To determine the role of protein kinase C in the regulation of intestinal fluid transport, experiments were performed with the rat jejunum in vivo, using the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (PMA), as stimulator of protein kinase C. Intraluminally administered PMA dose dependently reversed the net fluid absorption to net fluid secretion and significantly increased prostaglandin E2 (PGE2) but not 5-hydroxytryptamine (5-HT) output into the lumen. Mucosal cyclic AMP levels remained unchanged by PMA. Indomethacin inhibited the increase in PGE2 output and partially reduced the secretory response to PMA. Ketanserin was without effect whereas verapamil totally blocked the secretory response to PMA. It is concluded that intestinal fluid secretion, stimulated by activation of protein kinase C is partly mediated by PGE2 release. PGE2 may facilitate calcium entry rather than increase intracellular calcium through activation of cyclic AMP. Protein kinase C appears to play an important role as an intermediate in phosphoinositol hydrolysis, which is initiated by 5-HT, and finally induces fluid secretion via PGE2.

Animals↗
PubMed1990

5-HT2 and 5-HT3 receptor subtypes mediate cholera toxin-induced intestinal fluid secretion in the rat.

The mechanisms of diarrhea in Asiatic cholera have been studied extensively. Cyclic adenosine monophosphate, 5-hydroxytryptamine (5-HT), prostaglandins, and the function of neuronal structures have been implicated in the pathogenesis of cholera. To elucidate the action of 5-HT in mediating cholera secretion, in vivo experiments were performed in the rat jejunum. The inhibitory effects of the 5-HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ICS 205-930 were studied in cholera toxin- and 5-HT-induced fluid secretion. Both ketanserin and ICS 205-930 dose-dependently but only partially reduced the secretory effect of cholera toxin. The combination of the two blockers totally abolished cholera toxin-induced secretion without any influence on cholera toxin-induced increase in cyclic adenosine monophosphate. Prostaglandin E2- and bisacodyl-induced secretion was not affected by the combined administration of 5-HT2 and 5-HT3 antagonists. The present results provide evidence for an important role of 5-HT in cholera toxin-induced secretion. The data suggest a model in which cholera toxin may initiate the release of 5-HT from enterochromaffin cells. 5-Hydroxytryptamine may then cause prostaglandin E2 formation via 5-HT2 receptors and activation of neuronal structures via 5-HT3 receptors. These two effects may finally lead to the profuse fluid secretion which can be totally blocked by the combination of a 5-HT2 blocker and a 5-HT3 blocker.

Animals↗
PubMed1990

Influence on intestinal secretion of eicosanoids.

Eicosanoids have been shown to be important modulators of intestinal secretion. In cholera, cAMP is often regarded as the sole mediator, but recent data suggest that 5-hydroxytryptamine (5-HT) and prostaglandin (PG) E2 also play important roles. Thus cholera toxin (CT) increases their release from the rat jejunum in vivo, and human cholera is associated with an increased luminal 'overflow' of PGE2. In vitro evidence of secretion can be obtained with PG concentrations 100- to 1000-fold lower than those required for activation of the adenylate cyclase. Furthermore, 5-HT induces secretion associated with increased 'overflow' of PGE2, but without a change in mucosal cAMP. CT-induced release of PGE2 and fluid secretion can be decreased by indomethacin or by the 5-HT2-receptor antagonist, ketanserin, whereas the release of 5-HT and cAMP is not affected by either substance. Secretion caused by vasoactive intestinal polypeptide (VIP) is associated with increased mucosal cAMP levels, without a change in PGE2 release, and is unaffected by indomethacin and ketanserin. These results suggest that CT stimulates the release of 5-HT, which in turn causes the release of PGE2. The latter substances probably act via a local intramural reflex and contribute to secretion by mechanisms that are independent of cAMP.

Animals↗
PubMed1990

Stimulatory effects of 5-hydroxytryptamine on fluid secretion and transmural potential difference in rat small intestine are mediated by different receptor subtypes.

The rise in transmural potential difference (PD) and the fluid secretion induced by 5-hydroxytryptamine (5-HT) were measured in rat small intestine in-vivo. Both cisapride and ketanserin abolished the 5-HT-induced rise in systolic blood pressure mediated by 5-HT2 receptors. Cisapride inhibited the 5-HT-induced increases in the transintestinal PD, but over the same dose range it had no effect on the fluid secretion induced by 5-HT. In contrast, ketanserin caused a dose-dependent reduction in 5-HT-induced fluid secretion at doses that failed to influence the rise in PD. It is concluded that different receptors are responsible for the effects of 5-HT on fluid secretion and electrical activity in the rat small intestine.

Animals↗
PubMed1990

Comparison of the antisecretory effects of loperamide and loperamide oxide in the jejunum and the colon of rats in-vivo.

The antidiarrhoeal effect of loperamide is caused by its antimotility and antisecretory properties. In-vivo experiments in the rat jejunum and colon have been performed to compare the antisecretory effect of loperamide with the effect of its prodrug, loperamide oxide. Both loperamide and loperamide oxide administered intraluminally, equally and dose dependently (2 to 250 micrograms mL-1) reduced PGE2-induced net fluid secretion (32 ng min-1 i.a.) in the jejunum and colon. The antisecretory effect of both drugs is blocked by naloxone (1 mg kg-1 s.c.). It is concluded that loperamide oxide administered intraluminally is reduced to loperamide and has the same antisecretory potency as loperamide in jejunum and colon. The effect appears to be mediated via opiate receptors. The observation that loperamide cannot be detected in the colonic lumen two h after oral administration suggests that the drug is delivered from the blood stream to the site of action after absorption in the small intestine.

Administration, Oral↗
PubMed1989

Involvement of 5-hydroxytryptamine, prostaglandin E2, and cyclic adenosine monophosphate in cholera toxin-induced fluid secretion in the small intestine of the rat in vivo.

The diarrhea of cholera is considered to rely solely on a cyclic adenosine monophosphate-mediated secretory mechanism. However, both 5-hydroxytryptamine and prostaglandin E2 have been proposed to be involved in the pathogenesis of cholera. In vivo experiments were performed, therefore, in the rat jejunum to investigate the influence of purified cholera toxin on fluid secretion, luminal release of 5-hydroxytryptamine and prostaglandin E2, and formation of mucosal cyclic adenosine monophosphate. Also the effects of ketanserin, indomethacin, verapamil, and nifedipine on the named parameters were studied. Cholera toxin dose-dependently (0.1-0.5 microgram/ml) and time-dependently (1-5 h) increased mean net fluid secretion with a maximum response at 4 h. It also caused a significant (p less than 0.01) rise in release of 5-hydroxytryptamine and prostaglandin E2, in addition to formation of cyclic adenosine monophosphate. The dose-response curve for cholera toxin-induced fluid secretion was shifted to the right by indomethacin (10 mg/kg s.c.) and ketanserin (200 micrograms/kg s.c.), none of which caused a change in cholera toxin-induced release of 5-hydroxytryptamine. However, both agents significantly decreased the release of prostaglandin E2. Verapamil (0.2-9.5 micrograms/min i.a.) and nifedipine (0.05-0.5 microgram/min i.a.) dose-dependently reduced cholera toxin-induced fluid secretion. The estimated local concentrations at half-maximal inhibition were 5 x 10(-7) M verapamil and 5 x 10(-8) M nifedipine, respectively. The cholera toxin-induced increase in release of 5-hydroxytryptamine and prostaglandin E2 and formation of cyclic adenosine monophosphate was unaffected by verapamil. These results support the concept that cholera toxin-induced fluid secretion in vivo is caused, in part, by release of 5-hydroxytryptamine, which in turn stimulates formation of prostaglandin E2.

Animals↗
PubMed1988

Prostaglandin E2 is a mediator of 5-hydroxytryptamine induced water and electrolyte secretion in the human jejunum.

Studies in the rat jejunum in vivo have shown that 5-hydroxytryptamine (5-HT) causes secretion of fluid and luminal release of prostaglandin (PG) E2. These effects can be blocked by indomethacin and ketanserin, which suggests that PGE2 may be an important intermediate in the transduction mechanism leading to 5-HT induced fluid secretion. To test this hypothesis in man 'steady state' perfusions (9 ml/min) were done in eight healthy volunteers using the triple lumen technique. The proximal jejunum was perfused with Ringer's solution which contained 51Cr-EDTA as a non-absorbable marker. Before and after the administration of indomethacin (1.0 mg/kg iv) the effects of exogenous 5-HT (10 micrograms/kg/min iv) on jejunal net transport of fluid and electrolytes and jejunal flow rate (JFR) of PGE2 were measured in 15-min periods for 2 x 60 minutes after a 60 minute control period. 5-HT reversed fluid and electrolyte absorption into profuse secretion (p less than 0.01, Duncan's multiple range test) and significantly increased JFR of PGE2 (p less than 0.01). Indomethacin partly restored fluid and electrolyte absorption (p less than 0.01) and inhibited JFR of PGE2 (p less than 0.05). These results provide further evidence in favour of the theory that PGs are involved in 5-HT induced intestinal fluid secretion.

Adult↗
PubMed1988

Prostaglandin-mediated action of sennosides.

The aim of this study was to investigate whether prostaglandins (PG) are involved in the mediation of sennoside-induced colonic fluid and electrolyte secretion. Oral administration of senna pod extract dose-dependently reversed net absorption of water, sodium and chloride to net secretion, increased potassium secretion and stimulated the release of PGE2 into the colonic lumen. Inhibition of PG biosynthesis by pretreatment of the rats with indomethacin significantly inhibited the effects of senna pod extract both on net fluid transport and on PGE2 release. The inhibitory effect of indomethacin on net fluid transport induced by senna pod extract was dose-dependent. It is concluded that sennosides exert their laxative action at least partially via stimulation of colonic fluid and electrolyte secretion, and that this secretion is mediated by stimulation of endogenous PGE2 formation.

Animals↗
PubMed1987

Barbiturate poisoning and gastrointestinal propulsion.

Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.

Animals↗
PubMed1986

Significance of calcium for the prostaglandin E2-mediated secretory response to 5-hydroxytryptamine in the small intestine of the rat in vivo.

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.

Animals↗
PubMed1985

Neuropeptide Y (NPY) and peptide YY (PYY) inhibit prostaglandin E2-induced intestinal fluid and electrolyte secretion in the rat jejunum in vivo.

NPY, a recently discovered peptide consisting of 36 amino acids, is present in intrinsic intestinal nerves and in extrinsic noradrenergic nerves innervating intestinal blood vessels. We have investigated the influence of NPY and of the structurally related peptide YY (PYY) on the effect of PGE2-induced fluid and electrolyte secretion in the tied-off rat jejunum in vivo. Close intraarterial infusion of PGE2 (4.5-450 pmol X min-1) dose dependently reversed the net absorption of fluid, sodium and chloride into net secretion (P less than 0.01 for all three parameters). Additional i.a. infusion of NPY significantly inhibited the effect of PGE2 (45 pmol X min-1) on fluid transport at infusion rates of 0.4 and 4.0 pmol X min-1 (P less than 0.01). Infusion of 0.04 pmol X min-1 NPY was without effect. PGE2-induced sodium and chloride secretion were also significantly reduced by NPY at an infusion rate of 0.4 but not of 0.04 pmol X min-1. NPY alone was without any effect on fluid or electrolyte absorption in the controls. PYY, which is present in endocrine cells but not in nerves in the gut, was without effect at 0.4 pmol X min-1 and slightly but significantly reduced PGE2-induced fluid secretion at 4.0 pmol X min-1. It is concluded that NPY is a potent inhibitory factor in the neuronal control of intestinal fluid and electrolyte transport.

Animals↗
PubMed1985

Parathion and gastrointestinal transit in the rat.

The possibility of in vivo or post-mortem acceleration of gastrointestinal transit was investigated in the rat after sublethal or lethal doses of the insecticide parathion. Parathion did not change gastrointestinal transit time before or after death in the poisoned rat.

Animals↗
PubMed1985

Influence of chronic bisacodyl treatment on the effect of acute bisacodyl on water and electrolyte transport in the rat colon.

Excessive or unnecessary taking of laxatives leads to a vicious circle with perpetuation of laxative abuse and increase of laxative dosage, accompanied by severe clinically evident disturbances. It was investigated in rats whether chronic administration of bisacodyl reduces the effects of acute bisacodyl administration on net water and electrolyte flux in the rat colon transport in-vivo. After chronic pretreatment with bisacodyl had been given for 21 days (3 mg and 10 mg kg-1 day-1), net water and sodium absorption was found to be decreased whereas potassium secretion was increased. After 21 days of pretreatment, the effect of acute bisacodyl (10 micrograms ml-1 intraluminal) on net water and sodium transport was reduced whereas the effect on potassium secretion remained unchanged. Serum and erythrocyte levels of sodium and potassium remained unchanged in chronically pretreated rats. Serum aldosterone levels were enhanced two fold. It is concluded that under the experimental conditions described, chronically administered bisacodyl leads to elevated serum aldosterone which counteracts the effect of bisacodyl on net water and sodium transport but acts synergistically with bisacodyl on the effect on potassium loss.

Aldosterone↗