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M Jodal

Publications and source records attributed to M Jodal.

At least 19 recordsLinked to original sources
PubMed1992

Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion.

The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists were tested in rats in vivo on the intestinal fluid secretion evoked by cholera toxin. Five receptor antagonists were used, namely 2-bromolysergic acid diethylamine (2-bromo-LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were used in doses that inhibited the arterial hypertension and/or bradycardia evoked by 5-HT given i.v. Granisetron and ondansetron markedly diminished cholera-toxin-evoked secretion, whereas ketanserin was without any effect. Methysergide also diminished cholera-toxin-induced fluid secretion particularly when the drug was given as an i.v. infusion. The results are considered in relation to the pathophysiology of cholera secretion and to the current views of receptor subtypes for 5-HT. It is proposed that the receptor involved is a 5-HT3 receptor, possibly also a receptor of the 5-HT1 type. Results from experiments in which 5-HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion suggest that the 5-HT3 receptor is located in the villus tissue. It was also demonstrated that zimeldine, an inhibitor of presynaptic 5-HT reuptake, diminished choleraic secretion, an effect that may be ascribed to a 5-HT tachyphylaxis caused by an accumulation of 5-HT in a synaptic cleft.

Animals↗
PubMed1991

On the mechanisms of the basal alkaline secretion in the rat ileum in vivo.

Basal alkaline secretion of the denervated rat ileum was monitored by a pH-stat method. Changes of transepithelial electrical potential difference (PD) were also continuously registered. In other experiments net fluid transport was measured with a gravimetric method. The importance of the enteric nervous system for the recorded variables was investigated by giving i.v. hexamethonium, neuropeptide Y (NPY) or methionine-enkephalin or by stimulating electrically the mesenteric nerves surrounding the superior mesenteric artery. Alkaline secretion was inhibited by about 20% by mesenteric nerve stimulation or by neuropeptide Y (NPY) or met-enkephalin i.v. A somewhat greater inhibition (approximately 30%) of transepithelial electrical potential difference was elicited by the mesenteric nerve stimulation and NPY whereas met-enkephalin did not cause any transepithelial electrical potential difference change. Net fluid absorption was markedly diminished (by approximately 65-75%) by met-enkephalin but not by NPY. The cellular mechanisms underlying alkaline secretion were investigated by means of amiloride, SITS and acetazolamide. The basal alkaline secretion and transepithelial electrical potential difference were not influenced by 10(-3)M or 10(-4) SITS. In contrast 10(-3) M amiloride caused a significant increase of alkaline secretion but not of transepithelial electrical potential difference. A 35% reduction in the alkaline secretion but not transepithelial electrical potential difference was observed after acetazolamide had been given intravenously. A similar decrease was observed after giving hexamethonium. We conclude: (1) Enteric nerves are of comparatively small importance in controlling the ileal alkaline secretion recorded during basal conditions; (2) About 35% of the basal ileal alkaline secretion is carbonic anhydrase dependent. This mechanism is not influenced by nicotinic receptor blockade; (3) Under the present experimental conditions there may be an alkaline secretion which is concealed by a simultaneously operating Na+/H+ exchanger and; (4) No consistent quantitative correlation exists between alkaline secretion, transepithelial electrical potential difference and net field transport in the denervated rat ileum.

Acetazolamide↗
PubMed1991

Tissue osmolality in intestinal villi of four mammals in vivo and in vitro.

Using a freezing point depression method osmolality in the intestinal tissue of four mammals (gerbils, guinea-pigs, rabbits and rats) was estimated in vivo, during fluid transport from an isotonic electrolyte-glucose solution. Net fluid transport was also measured. In gerbils, guinea-pigs and rabbits tissue osmolality was also estimated during in vitro conditions. A marked hyperosmolality was observed in vivo in the upper parts of the villi of all four mammals studied. The tissue osmolality was significantly higher than that seen in the same species during in vitro conditions. A villus hyperosmolality was observed also in species which exhibited a net fluid secretion (guinea-pig, rabbit ileum), indicating that the fluid secretion emanated from the intestinal crypts. Based on the results of the present experiments and on observations made in earlier experiments performed on the cat, it is proposed that the villus hyperosmolality is created by a countercurrent multiplier present in the intestinal villus. The hyperosmolar compartment in the villus tissue creates the force that drives fluid from lumen to tissue.

Animals↗
PubMed1990

Neuronal influence on intestinal transport.

Reflex activation of the enteric nervous system (ENS) from the intestinal lumen and also from the serosa induces intestinal secretion. Thus mechanical distention, cholera toxin, heat-stable enterotoxin from E. coli, bile acids, mucosal inflammation and chemical peritonitis all induce an intestinal secretion that is inhibited by 60-100% by nerve-blocking agents. As a result of a large number of in vitro and in vivo studies, a picture of the organization of the secretory enteric nervous reflexes is now emerging. In secretory states with preserved intact intestinal epithelium, it is proposed that the reflex activation occurs via stimulation of receptor cells, i.e. epithelial endocrine cells such as EC and N-cells, which release peptides/amines into the interstitial space and thereby activate nerves close to the epithelium. The afferent neurones appear to transfer the reflex to the myenteric plexus, probably by using tachykinins as transmitters. This is in agreement with a superior and co-ordinating role for the myenteric plexus in the control of intestinal function by the ENS. Interneurones in turn mediate the transmission of the nerve signal to the submucosal plexus and the efferent neurones via cholinergic, nicotinic postganglionic receptors. The transmitters at the effector cells are acetylcholine and probably VIP.

Afferent Pathways↗
PubMed1990

Studies of cholera toxin-induced changes of alkaline secretion and transepithelial potential difference in the rat intestine in vivo.

A pH-stat technique was used to investigate the effects of cholera toxin (CT) on alkaline secretion from denervated intestines (jejunum, ileum, colon) in anaesthetized rats. Transepithelial potential difference (PD) was also followed in some experiments. CT, given intraluminally, caused a marked increase in jejunal alkaline secretion, whereas only a small effect was observed in the ileum and no apparent effect was noted in the proximal colon. The pronounced increase in jejunal alkaline secretion was found to be inhibited by 10-25% by hexamethonium (10 mg kg-1 body wt i.v.) and similarly by serosal application of lidocaine, whereas atropine (0.25 mg kg-1 body wt i.v.) had no effect. Thus the cholera toxin-induced alkaline secretion in the jejunum is attributed mainly to a non-nervous mechanism. The small effect of CT on ileal alkaline secretion observed in this study contrasts with the high ileal bicarbonate concentration reported in cholera by authors who estimated the concentration from the total carbon dioxide/bicarbonate contents. This discrepancy may be explained by a CT-evoked increased transport of the coupled Na+/H+ and Cl-/HCO3- exchangers, which cannot be measured with the pH-stat technique used in this study.

Animals↗
PubMed1990

Intestinal fluid transport in the small intestine of normotensive and spontaneously hypertensive rats: the importance of enteric nerves, chloride and bicarbonate secretion.

Fluid transport was studied in periarterially denervated jejunal segments of spontaneously hypertensive rats (SHR) of the Okamoto strain and as a control also in Wistar-Kyoto rats (WKR). In agreement with the findings of an earlier report a 'spontaneous' fluid secretion was observed in SHR whereas the intestinal segments of WKR absorbed fluid. The fluid secretion in SHR was inhibited by tetrodotoxin or lidocaine placed on the serosal surface of the intestinal segment under study. These observations confirm our earlier proposal that secretory nervous pathways in the enteric nervous system evoke the fluid secretion in SHR. In an attempt to analyse the cellular mechanisms that underlie the fluid secretion in SHR the animals were given loop diuretics in doses that evoked diuresis. No effect on intestinal fluid transport was seen in SHR or WKR. Furthermore, to study the importance of bicarbonate transport alkaline secretion was monitored with a pH-stat technique. In the initial part of the experiments the alkaline secretion in SHR and WKR was similar. In half of the SHR experiments alkaline secretion increased with time. This increase could be completely reversed with hexamethonium and atropine (only tested in three experiments). The time course of the alkaline and fluid secretion in SHR did not coincide, indicating that bicarbonate ion transport was not the major cause of fluid secretion in SHR. In agreement with this conclusion it was observed that acetazolamide (a blocker of carbonic anhydrase) did not influence rate of fluid transport in SHR or WKR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

On the role of vasoactive intestinal polypeptide and tachykinins in the secretory reflex elicited by chemical peritonitis in the cat small intestine.

Peritonitis induced by serosal application of 0.1 M hydrochloric acid causes net fluid secretion via the enteric nervous system. The aim of the present study was to investigate the roles of vasoactive intestinal peptide (VIP) and tachykinins in this reflex(es). The release of tachykinins (substance P [SP], neurokinin A [NKA], neuropeptide K [NPK]) and VIP into the mesenteric circulation, net fluid transport, intestinal blood flow and sometimes motility were recorded simultaneously in extrinsically denervated jejunal segments of the cat in vivo. The release of both VIP and NKA was increased upon application of HCl to the cat jejunal serosa. Tetrodotoxin, hexamethonium and methionine enkephalin inhibited both the induced VIP release and the secretory response. The increased release of NKA was unaffected by hexamethonium. We propose that the intramural secretory reflex evoked by acid application of the serosa consists of an 'afferent' tachykinin neuron, a cholinergic interneuron and an 'efferent' VIPergic neuron innervating the secretory enterocytes.

Animals↗
PubMed1990

Further studies of the changes in alkaline secretion, transepithelial potential difference and net fluid transport induced by the heat-stable enterotoxin of Escherichia coli (STa) in the rat jejunum in vivo.

A pH-stat technique was used to study the mechanisms underlying the intestinal alkalinization evoked by the heat-stable enterotoxin of Escherichia coli (STa) in the rat denervated jejunum in vivo. In addition, concomitant changes of transepithelial potential difference and fluid transport were also investigated. To test the possible involvement of the enteric nervous system in the STa-stimulated alkaline secretion and potential difference, the mesenteric nerves were electrically stimulated or neuropeptide Y or methionine-enkephalin was infused intravenously. None of these interventions inhibited to any large extent the STa-stimulated alkaline secretion, whereas a greater suppression was noted on the concomitantly increased potential difference. Furthermore, neuropeptide Y but not methionine-enkephalin significantly inhibited STa-induced jejunal fluid secretion although neuropeptide Y was without effect on basal fluid transport. It is concluded that the enteric nervous reflex(es) which are of significant importance in explaining STa-evoked fluid secretion plays a minor role in controlling alkaline secretion. Furthermore, alkaline secretion may not contribute to the increase in potential difference caused by STa Amiloride (10(-4) or 10(-3) M) had no effect on the STa-stimulated alkaline secretion, implying that some cellular mechanism other than an inhibition of Na+/H+ exchanger explains the observed response. Similarly, acetazolamide had no effect on the STa-stimulated alkaline secretion or potential difference, suggesting that the secreted alkaline is of extracellular origin rather than from the cellular metabolism in the enterocytes.

Animals↗
PubMed1990

Effects of heat-stable Escherichia coli enterotoxin on intestinal alkaline secretion and transepithelial potential difference in the rat intestines in vivo.

The effects of the heat-stable enterotoxin of Escherichia coli (STa) on intestinal alkaline secretion and transepithelial electric potential difference (PD) were investigated in vivo in denervated segments of rat jejunum, ileum, and proximal colon. STa caused a significant increase in alkaline secretion in the jejunum but not in the ileum or colon. The jejunal effect of STa may be ascribed to a stimulation of bicarbonate secretion and/or an inhibition of Na+/H+ exchange. With regard to PD, STa caused a marked rise in colonic PD, whereas only a small response was found in the jejunum. No effect on PD was seen in the ileum. Hexamethonium (10 mg/kg intravenously) significantly diminished the effects of STa on PD, whereas only a small inhibition of the STa-induced alkaline secretion was observed. The effect of lidocaine on PD and alkaline secretion was found to be similar to that of hexamethonium. Atropine had no effect on any of the studied variables. These findings suggest that STa exerts, via nerves, a profound influence on the jejunal transport mechanisms responsible for the changes in PD, whereas the influence on alkaline secretion is to a large extent not mediated via enteric nerves. Thus, the extent of enteric nervous control of epithelial function differs for different transport functions. The findings also indicate that the bicarbonate ion is not the anion mainly responsible for the fluid secretion elicited by STa.

Animals↗
PubMed1989

Effects of cholera toxin, Escherichia coli heat stable toxin and sodium deoxycholate on neurotensin release from the ileum in vivo.

Neurotensin (NT) is a biologically active peptide found in specialized epithelial cells (N-cells) in the distal small intestine. In this study we tested the hypothesis that NT may be released by luminal secretagogues, i.e., cholera toxin, Escherichia coli heat-stable toxin and sodium deoxycholate. Cholera toxin elicited net fluid secretion in anesthetized cats. This secretion was accompanied by an increased release of NT-like immunoreactivity (NTLI) into the mesenteric vein when NTLI was measured with either a C-terminally or a N-terminally directed antibody. An increasing plasma NTLI concentration (N-terminally directed antibody) was recorded in the mesenteric vein and femoral artery in cholera experiments. These results indicate that cholera toxin releases NT from the small intestine. Since neurotensin causes intestinal fluid secretion at least in part via an activation of enteric nerves we propose that the N-cell functions as a 'receptor cell' which activates an intramural secretory reflex upon luminal stimulation by cholera toxin. This study does not support a similar role for NT in the secretion elicited by the heat stable toxin of Escherichia coli or by sodium deoxycholate since we were unable to demonstrate any intestinal release of NTLI after exposing the intestine to these secretory agents.

Animals↗
PubMed1989

Evidence for a countercurrent exchanger in the intestinal villi of suckling swine.

The possible existence of a countercurrent exchanger (multiplier) in the intestinal villi of suckling swine was investigated with three different methods: (1) Comparing venous appearance of oxygen and red cells in the mesenteric vein after close i.a. injection of a blood sample equilibrated with pure oxygen and containing methaemoglobinaemic red cells. (2) Determining sodium (micrograms) over protein (mg) ratios along villi. (3) Estimating tissue osmolality in the villus tissue from measurements of freezing-point depression. It was observed that oxygen appeared earlier than red cells in the mesenteric vein after i.a. injection. Furthermore, both the chemical measurements of sodium/protein ratios in the villi and the estimations of tissue osmolality indicate that there exists a gradient of osmolalities along the villus length, the villus tip being hyperosmolar as compared to the villus base. We conclude that a countercurrent exchanger (multiplier) exists in the villi of suckling swine. Its possible pathophysiological significance is discussed.

Animals↗
PubMed1988

The effect of splanchnic nerve stimulation and neuropeptide Y on cholera secretion and release of vasoactive intestinal polypeptide in the feline small intestine.

The effect of sympathetic nerve stimulation and intra-arterial infusion of neuropeptide Y (NPY) on net fluid secretion and release of vasoactive intestinal polypeptide (VIP) was studied in the cat small intestine during a secretion due to cholera toxin. Activation of the splanchnic nerves (4 Hz, 5 ms, 5 V) decreased net fluid secretion to 57 +/- 10% of control. Concomitantly, the release of VIP was reduced to less than 50%. Furthermore, close i.a. infusion of NPY (estimated increase in plasma concentration 75 nmol l-1) reduced the net fluid secretion and VIP release to 27 +/- 5 and 28 +/- 4% of the pre-stimulatory value. The correlation between the decrease in net fluid secretion and reduction in VIP release showed a strong positive correlation (r = 0.83). These results strongly indicate that the antisecretory effect of sympathetic nerve stimulation during cholera diarrhoea is mediated by inhibition of secretory VIP neurons in the intestinal mucosa. A similar mechanism is also proposed for the intravascularly administered NPY.

Animals↗
PubMed1988

Somatostatin and methionine-enkephalin inhibit cholera toxin-induced jejunal net fluid secretion and release of vasoactive intestinal polypeptide in the cat in vivo.

A major part of the net fluid secretion that is elicited by cholera toxin in the small intestine of the cat has been shown to be mediated by intramural nervous reflex(es). The release of vasoactive intestinal polypeptide (VIP) from the small intestine is increased by cholera toxin. We report that close intra-arterial infusions of methionine-enkephalin (met-enk) and somatostatin cause a parallel reduction in cholera toxin-induced net fluid secretion and in VIP release from the small intestine of the cat. Intestinal blood flow was slightly, but significantly increased by met-enk and not influenced by somatostatin. These results strengthen the hypothesis that VIP is involved as a neurotransmitter in the nervous reflex mediating cholera toxin-induced secretion.

Animals↗
PubMed1988

The importance of the subepithelial resistance for the electrical properties of the rat jejunum in vitro.

The aim of the study was to evaluate full-thickness and partially stripped jejunum as a model for neurogenic control of electrogenic ion transport. The electrical properties of full-thickness and partially stripped segments were studied in Ussing chambers. Using square-pulse analysis, subepithelial and epithelial resistances (Rs and Rp) were determined, and by compensating for the potential fall across Rs, the current generated by the epithelium could be measured. In full-thickness tissue, Rs was approximately 80% of total tissue resistance, and the current measured during short-circuiting of the whole tissue (SCC) was therefore only 20-25% of the current generated by the epithelium (Im). Surgical stripping of the tissue decreased Rs by 10-20%. This means that in full thickness as well as in stripped tissue, 70-80% of the potential difference across the epithelial layer remains after traditional 'short circuiting'. Over a 25-min period, none of the electrical parameters changed significantly in the full-thickness tissues. In the stripped group PD, SCC and Im fell significantly, and in parallel during the same period of time. Neither glucose, noradrenaline, met-enkephalin or carbachol had any significant effect on Rs, Rp or the Rs/Rp ratio. The relative effects of these agents on Im and SCC were therefore similar. Substance P and VIP increased the Rs/Rp ratio significantly and, therefore, the effect of these drugs on Im was significantly more pronounced than the effect on SCC. The results show that the subepithelial resistance must be taken into account when the electrogenic activity in the epithelium is to be determined correctly. Conventionally measured SCC reflects the electrogenic effect of the tested putative neurotransmitters, but the magnitude of the responses is grossly underestimated, particularly for substance P and VIP.

Animals↗
PubMed1987

Changes in cyclic 3'5'-adenosine monophosphate tissue concentration and net fluid transport in the cat's small intestine elicited by cholera toxin, arachidonic acid, vasoactive intestinal polypeptide and 5-hydroxytryptamine.

We have analysed tissue cyclic 3'5'-adenosine monophosphate (cAMP) concentration in different fractions of the cat's small intestinal mucosa during secretion elicited in vivo by four different secretagogues: cholera toxin (administered intraluminally), vasoactive intestinal polypeptide (VIP; given i.a.), arachidonic acid (AA; administered intraluminally) and 5-hydroxytryptamine (5-HT; given i.a.). Cholera toxin was found to increase cAMP concentration in the villi but not in the crypts. The VIP, AA and 5-HT did not influence tissue cAMP concentration despite a profuse net fluid secretion. Hexamethonium inhibited secretion elicited by cholera toxin and AA but did not significantly influence tissue cAMP concentration. There is strong evidence for the view that villus and crypt regions of the small intestinal mucosa have different functions, secretion taking place in the crypts and absorption in the villi. However, the lack of cAMP increase in the crypts reported in this study suggests that cholera toxin in this model does not reach the crypts. The results are not in agreement with a role for cAMP in mediating secretion from the crypts, but are compatible with a role of cAMP in inhibiting absorption in the villi. It is suggested that the observed fluid secretion from the crypts elicited by cholera toxin, AA and 5-HT is to a major part mediated by intramural enteric reflexes.

Animals↗