Biomedical subjects

E Scharrer

Publications and source records attributed to E Scharrer.

At least 19 recordsLinked to original sources

PubMed1996

Intraportal infusion of 2,5-anhydro-D-mannitol increases afferent activity in the common hepatic vagus branch.

Peripheral administration of the fructose analogue 2,5-anhydro-D-mannitol (AM), that inhibits hepatic glucose release and ATP formation, stimulates food intake in rats. This effect is partly generated in the hepato-portal area and transmitted to the central nervous system by the common hepatic vagus branch because hepatic branch vagotomy eliminated the feeding response to AM. In the present study, we investigated if the pertinent signal to increase food intake changes the discharge rate in hepatic vagal afferents. An in vivo preparation was used to record afferent hepatic vagal activity following intraportal infusion of AM in anaesthetized rats. Fine nerve filaments were isolated from the distal cut end of the hepatic vagus branch. Nerve activity was recorded by a bipolar electrode and analyzed after conversion of raw data to standard pulses. Standard pulses were integrated into spike counts of 5 s duration and the mean number of spikes in a 50 s interval at baseline was compared to spike count 10, 30 and 50 min after infusion of AM (100 or 300 mg/kg) or saline (control). Saline infusion did not influence afferent hepatic vagal activity. Intraportal infusion of AM, however, dose-dependently increased afferent activity in the hepatic vagus branch. In conclusion, AM increased the afferent discharge rate in the common hepatic vagus branch at doses that have previously been shown to increase food intake. These findings agree with the proposed role of fuel metabolism in the hepato-portal area in the control of food intake and with the suggestion that fuel availability controls food intake by influencing the hepatic afferent discharge rate.

Animals↗

PubMed1996

Modulation by fish oil diet of eicosanoid-induced anion secretion in the rat distal colon.

Eicosanoids are involved in the mediation of inflammatory and allergic processes in the gut. In order to evaluate a potential beneficial effect of the diet, the effect of mediators of inflammation and of a sensitization against egg albumin on anion secretion across the colon was tested using rats fed on a diet containing 15% fish oil as compared to 15% olive oil as donor animals. Feeding on a fish oil diet significantly reduced the response to bradykinin or phospholipase C, known agonist of prostaglandin-induced secretion, by about 50%. The increase in short-circuit current (Isc) induced by the phospholipase A2 stimulator, melittin, or by distension of the gut wall were only insignificantly inhibited by 15-30%. Administration of egg albumin to the mucosas from animals sensitized against egg albumin induced an indomethacin- and tetrodotoxin-sensitive increase in Isc. This response was, however, only insignificantly (30%) reduced by the fish oil diet. In conclusion, the effect of fish oil diet depends on the stimulus used for activation of prostaglandin release. This suggested that different pools of arachidonic acid are differentially affected by the diet or that certain stimuli for phospholipases are strong enough to overcome the effect of a reduced substrate availability. Consequently, a diet rich in polyunsaturated n-3 fatty acids may only play an adjuvant role for the therapy of inflammatory or allergic intestinal diseases.

Acid-Base Equilibrium↗

PubMed1996

Segmental heterogeneity of swelling-induced Cl- transport in rat small intestine.

The effect of cell swelling induced by hypotonic media was studied in segments of rat small intestine. In the Ussing chamber, exposure to a hypotonic medium caused a decrease in short-circuit current (Isc) and potential difference (Vms) in the jejunum, whereas the ileum responded with an increase in Isc and Vms. The transition from one pattern to the other was located about in the middle of the small intestine. Tissue conductance decreased in both segments, probably due to a reduction of paracellular shunt conductance induced by the cell swelling. Voltage scanning experiments revealed that the observed decrease in total tissue conductance in the ileum was caused solely by a decrease in local conductance in the villus region while the crypt conductance did not change, suggesting that the decrease in paracellular conductance of the crypts is compensated by an increase in cellular conductance. The response in both segments was dependent on the presence of Cl- and was blocked by the Cl- channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). It was not affected by the neurotoxin tetrodotoxin. In the jejunum the swelling-induced decrease in Isc was reduced in the presence of the cyclooxygenase inhibitor, indomethacin, or the lipoxygenase inhibitor, nordihydroguaiaretic acid. In the ileum the Cl- secretion induced by hypotonicity was blocked by the K+ channel blocker quinine and was reversed into a decrease in Isc when serosal Ca2+ was zero. We conclude that the observed volume regulatory changes are initiated in the jejunum by an eicosanoid-mediated opening of basolateral Cl- channels and in the ileum by a Ca2+-mediated opening of K+ channels which enhances apical Cl- efflux.

Animals↗

PubMed1996

Inhibition of food intake in rats by the K+ channel opener cromakalim.

We studied the effect of the K+ channel opener cromakalim, which exhibits antihypertensive properties, on food intake in rats. Intraperitoneally injected cromakalim induced a dose-dependent (0.1, 0.5, and 1.0 mg/kg body wt.) reduction in food intake, which was associated with an inhibition of gastric emptying. The anorectic effect was not influenced by subdiaphragmatic vagotomy. Cromakalim's anorectic effect did not appear to be due to a learned taste aversion. Therefore, an intact abdominal vagus is not a prerequisite for cromakalim's anorectic effect.

Animals↗

PubMed1996

Attenuation of the anorectic effects of glucagon, cholecystokinin, and bombesin by the amylin receptor antagonist CGRP(8-37).

The anorectic effect of IP injection of amylin (1 microgram/kg) was abolished by simultaneous IP injection of the amylin receptor antagonist calcitonin gene-related peptide-(8-37) [CGRP(8-37), 10 micrograms/kg]. The IP injection of pancreatic glucagon (400 micrograms/kg) at dark onset also reduced food intake in 24-h food-deprived rats, and this effect was also totally blocked by coadministration of CGRP(8-37) (10 micrograms/kg). In another feeding paradigm with glucagon (540 micrograms/kg IP 3 h into the light phase in 3 h-prefed rats), however, the anorectic effect of glucagon was not significantly antagonized by CGRP(8-37). The anorectic effect of cholecystokinin (CCK) (0.25 microgram/kg) and bombesin (BBS) (2 micrograms/kg) was partly neutralized by CGRP(8-37). In contrast, the anorectic effect of vasopressin (VP) (2.5 micrograms/kg) was not influenced by CGRP(8-37). As glucagon has been shown previously to increase the secretion of amylin, we conclude that the anorectic effect of peripherally administered glucagon is mediated by the release of amylin, at least under certain conditions. This may also be true for CCK and BBS, as these peptides are insulinotropic and may therefore be presumed to increase amylin release.

Amyloid↗

PubMed1996

The histaminergic, but not the serotoninergic, system mediates amylin's anorectic effect.

In the present study, we investigated the influence of blockade of the serotoninergic and histaminergic neurotransmitter system on the anorectic effect of IP-injected amylin in rats. In 12- or 24-h food-deprived rats, blockade of central and peripheral serotonin (5-HT) receptors with the 5-HT1 and 5-HT2 receptor antagonist metergoline (0.5 or 0.05 mg/kg, IP, respectively) did not seem to influence the anorectic effect of IP injected amylin (1 microgram/kg). Similarly, inhibition of 5-HT synthesis and release with the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (200 micrograms/kg, IP) did not diminish amylin's (5 micrograms/kg, IP) anorectic effect in 24-h food-deprived rats whereas that of CCK (3 micrograms/kg, IP) was blocked under comparable conditions. Pretreatment of rats with the histamine H3 receptor agonists R-alpha-methylhistamine (MH: 3 mg/kg, IP) and Imerit (3 mg/kg, IP), which block transmission in the histaminergic system by inhibiting release of endogenous histamine, attenuated amylin's (1 microgram/kg) anorectic effect in 24-h food-deprived rats. These results suggest that the histaminergic system in involved in transduction of IP amylin's inhibitory effect on feeding in rats. In contrast, the serotoninergic system does not seem to be involved in mediating amylin's anorectic effect.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1996

Neuronally mediated anion secretion induced by short-chain fatty acids in the rat distal small intestine.

The short-chain fatty acids acetate, propionate and butyrate induced a concentration-dependent increase of short-circuit current (Isc) in the rat distal small intestine in vitro. They were ineffective in the proximal small intestine. The increase of lsc in the distal small intestine was dependent on the presence of Cl- and HCO3- ions. It was blocked by the inhibitor of the Na(+)-K(+)-Cl(-) -cotransporter, bumetanide, and by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate, indicating that short-chain fatty acids evoke an anion secretion. The secretion induced by propionate was blocked by the neurotoxin, tetrodotoxin, and inhibited by the muscarinic antagonists, atropine. In contrast, indomethacin, a cyclooxygenase inhibitor, or nordihydroguaiaretic acid, a lipoxygenase inhibitor, were ineffective. These results indicate that short-chain fatty acids stimulate chemosensitive neurones in the rat small intestine in a region-specific manner, which induce anion secretion by the release of mainly acetylcholine.

Animals↗

PubMed1996

Cyclic AMP-dependent regulation of K+ transport in the rat distal colon.

1. The effect of agonists of the cyclic AMP pathway and of 293B, a chromanole-derived K+ channel blocker, on K+ transport in the rat distal colon was studied by measuring unidirectional fluxes, uptake, and efflux of Rb+ in mucosa-submucosa preparations and by patch-clamp of crypt epithelia from isolated crypts. 2. 293B concentration-dependently inhibited basal and forskolin-stimulated short-circuit current. In isolated crypts 293B blocked a basal K+ conductance but had no effect on cyclic AMP-evoked depolarization induced by the opening of apical Cl- channels. When the effect of cyclic AMP on Cl- conductance was prevented by substituting Cl- with gluconate, an inhibition of total cellular K+ conductance by forskolin and a membrane-permeable cyclic AMP analogue was unmasked. 3. Unidirectional ion flux measurements revealed that 293B suppressed the increase in JRbsm induced by forskolin. This, together with the inhibition of cyclic AMP-induced anion secretion indicates that the drug blocks K+ channels, presumably both in the apical and the basolateral membrane. Forskolin caused not only inhibition of K+ absorption, but also stimulation of K+ secretion. The inhibition was diminished, but not blocked, in the presence of inhibitors of the apical H(+)-K(+)-ATPase, vanadate and ouabain. Forskolin stimulated serosal, bumetanide-sensitive Rb+ uptake, whereas mucosal, ouabain/vanadate-sensitive uptake remained unaffected. 4. Efflux experiments revealed that forskolin caused a redistribution of cellular K+ efflux reducing the ratio of basolateral versus apical Rb+ efflux. 5. These results suggest that intracellular cyclic AMP exerts its effects on K+ transport by several mechanisms: an increase in the driving force for K+ efflux due to the depolarization induced by opening of Cl- channels, a stimulation of the basolateral uptake of K+ via the Na(+)-K(+)-Cl(-)-cotransporter, and a decrease of the ratio of basolateral versus apical K+ conductance leading to an enhanced efflux of K+ into the lumen and a reduced K+ efflux to the serosal compartment.

Animals↗

PubMed1996

Hepatic branch vagotomy enhances feeding in response to centrally elicited glucose deprivation in rats.

Intracerebroventricular (I.C.V.) administration of 2-deoxy-D-glucose (2-DG) produces glucose deprivation-induced ('glucoprivic') feeding and sympathoadrenal activation. To find out whether peripheral mechanisms modulate centrally elicited glucoprivic feeding the effect of hepatic branch vagotomy (HBV) compared with sham vagotomy (SV) on the feeding response to I.C.V.-injected 2-DG (1.2 or 2.4 mg per rat) was tested in rats fed a fat-enriched diet (18% fat). 2-DG was injected into the lateral ventricle 1 h after after dark onset, at light onset or 6 h after light onset of the 12 h light-12 h dark cycle. Apart from one (1.2 mg 2-DG injected 1 h after dark onset) out of six experiments, HBV enhanced glucoprivic feeding. This finding is consistent with the assumption that centrally elicited glucoprivic feeding is antagonized by peripheral stimuli signalled to the brain through the hepatic vagus branch.

Animals↗

PubMed1996

Cinnamate uptake by rat small intestine: transport kinetics and transepithelial transfer.

Due to their ubiquitous occurrence in the plant kingdom, plant phenolics, including monomeric cinnamic acids, are ingested by man and animals in variable amounts with their natural diets. Recently, Na(+)-dependent saturable transport of cinnamic acid across the brush-border membrane of rat jejunum has been described. It was the aim of the present study to characterize this mechanism in more detail. We therefore determined the transport kinetics of mucosal uptake of radioactively labelled cinnamic acid under various conditions using a short-term mucosal uptake technique. In addition, the transfer of cinnamic acid across the jejunal wall was investigated using everted intestinal sacs. Investigations of the kinetics of cinnamic acid uptake by the mid-jejunal mucosa revealed the involvement of two transport components, a diffusive Na(+)-independent mechanism and a saturable Na(+)-dependent mechanism. The results obtained with everted sacs provided further evidence of the existence of an active Na+ gradient-driven transport of cinnamic acid across the intestinal epithelium. In the presence of Na+, a significant accumulation of cinnamate occurred inside the serosal compartment and this was strongly inhibited by serosal ouabain. A decrease in the extracellular pH stimulated mucosal cinnamate uptake by increasing the apparent affinity (1/km). This may be attributable to the involvement of a transmembrane H+ gradient in Na(+)-dependent cinnamate transport because the protonophore FCCP caused a significant reduction of cinnamate uptake only in the presence of Na+. The kinetics of cinnamate transport in the absence or presence of a surplus of either unlabelled cinnamate or unlabelled butyrate indicates a reduction in the apparent affinity of the Na(+)-dependent mechanism involved in cinnamate uptake. These results may be explained by a modification of the mechanism by the intracellular pH. Additionally, competitive inhibition of cinnamate uptake by substances structurally related to cinnamic acid may also be involved.

Animals↗

PubMed1995

Hyperpolarization of the liver cell membrane by palmitate as affected by glucose and lactate: implications for control of feeding.

Since the membrane potential of liver cells being in contact with vagal afferents has been proposed to represent a major signal in metabolic control of food intake, we investigated the effect of palmitate, glucose and lactate on the membrane potential of hepatocytes with microelectrodes using superfused mouse liver slices. The mice used for the experiments were fed a fat-enriched diet (18% fat). Palmitate (0.5 mM) hyperpolarized the membrane of hepatocytes by 3-4 mV, and this hyperpolarization was not affected by 5-10 mM glucose and 0.5-1 mM lactate. Glucose alone did not influence the potential, even when mice fed a high carbohydrate diet were employed. At lactate concentrations > or = 2 mM the palmitate induced hyperpolarization was eliminated and 5 mM lactate or pyruvate alone hyperpolarized the liver cell membrane. Similar to the palmitate induced hyperpolarization, the lactate induced hyperpolarization was prevented by the K-channel blocker TEA, suggesting that activation of K channels is involved in the hyperpolarization. The results show that physiological concentrations of glucose and lactate do not affect the hyperpolarization of the liver cell membrane due to fatty acid oxidation. The implications of these findings with regard to control of food intake by fatty acid oxidation and lactate metabolism are discussed. The observations are consistent with a signal function of the hepatic membrane potential in physiological control of food intake by fatty acid oxidation. Hepatic lactate metabolism at supraphysiological lactate concentrations may also produce a satiety signal coded by the hepatic membrane potential.

Animals↗

PubMed1995

Meal pattern during the transient hypophagia of rats switched from a high fat to a high carbohydrate diet.

Meal pattern was investigated during the transient hypophagia lasting about 1 week when rats are switched from a carbohydrate-free high fat (HF) diet to an isocaloric high carbohydrate (HC) diet. After the HF/HC diet switch, voluntary food intake was suppressed through reduction of meal size with meal frequency remaining unaffected. Thus, the satiety ratio was increased in HF rats ingesting the HC diet. The observation that the first meal after the HF/HC switch, unlike the following meals, was not yet diminished, suggests that conditioning is involved in the reduction of meal size resulting from the switch. About 1 week after the dietary switch, the feeding pattern of rats had adjusted to that of rats receiving the HF diet. Unlike the HF/HC switch, the HC/HF switch did not reduce cumulative food intake, but decreased meal size and increased meal frequency during the first day. It is suggested that the transient decrease in meal size and increase in satiety ratio following the HF/HC diet switch arises partly from a relatively high postabsorptive satiating potency of glucose related to a low rate of glucose disposal found in previous work under such conditions. A transiently reduced gastrointestinal clearance of carbohydrate may also be involved.

Animals↗

PubMed1995

Circadian anorectic effects of peripherally administered amylin in rats.

The pancreatic peptide amylin (1 microgram/kg) injected intraperitoneally reduced cumulative food intake for up to 4 h in food-deprived (24 h) and non-deprived rats at various times of the day, i.e., at dark onset, in the middle of the dark phase, and at light onset. At none of these times did subdiaphragmatic vagotomy abolish the anorectic effect of amylin. Rather, vagotomy enhanced, by unknown mechanisms, amylin's anorectic effect in food-deprived rats at light onset and in the middle of the dark phase. In contrast to previous studies with older rats, amylin's anorectic effect was also observed when injected into nondeprived rats. The findings of the present study extend previous reports in that amylin's anorectic effect, not being abolished by abdominal vagotomy after intraperitoneal injection, can be elicited at different times of the day.

Amyloid↗

PubMed1995

Hyperpolarization of the cell membrane of mouse hepatocytes by fatty acid oxidation.

The effect of palmitate and metabolizable and nonmetabolizable monosacharides (D-glucose, D-fructose and 2-deoxy-D-glucose = 2-DG) on the membrane potential (Vm) of mouse hepatocytes was investigated employing a superfused mouse liver slice technique. Palmitate hyperpolarized the liver cell membrane in a concentration dependent manner whereas the monosaccharides tested did not. When mice were fed a fat-rich diet, the hyperpolarisation was greater in comparison to mice fed a low fat diet. The hyperpolarization was reversed by ouabain, an inhibitor of the Na+/K(+)-ATPase, by the K(+)-channel blockers tetra-ethyl-ammonium (TEA) and cetiedil and by three inhibitors of fatty acid oxidation (2-bromopalmitate, 2-bromooctanoate and 4-pentenoate). The results suggest that hyperpolarization of the liver cell membrane is due to fatty acid oxidation and that both activation of Na+/K(+)-ATPase and opening of K(+)-channels are involved. The implications of these findings with regard to control of food intake by fatty acid oxidation are discussed. The results are consistent with a role of the hepatic membrane potential in control of food intake by fatty acid oxidation.

Animals↗

PubMed1995

Amylin decreases meal size in rats.

Adult male rats were intraperitoneally (i.p.) injected with 1.0 microgram/kg amylin at the beginning of the dark phase in 24 h food deprived or undeprived rats, and a computerized system measured feeding behavior. In food deprived rats, amylin reduced the size of the first postdeprivation meal without affecting intrameal feeding rate or the size or timing of subsequent meals. The same pattern was observed in undeprived rats, but amylin also increased the latency to the first postinjection meal. In a conditioned taste aversion test, i.p. amylin (1 microgram/kg) injection just prior to rats' first access to a saccharine-flavored version of their maintenance diet, failed to affect their subsequent selection of that diet relative to the maintenance diet 2 d later. Finally, 2-min meal-contingent hepatic portal infusions of amylin (1-3.2 microgram/rat) during nocturnal spontaneous meals in undisturbed, ad lib fed rats reduced the meal size and meal duration, and increased the postprandial satiety ratio. Again, feeding rate and the size and duration of subsequent meals were not affected. These results suggest that amylin inhibits feeding by facilitating meal-ending satiety processes.

Amyloid↗

PubMed1995

Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin.

Amylin injected IP reduced food intake for 2-4 h in subdiaphragmatically vagotomized and in sham-vagotomized rats. The magnitude of the anorectic effect of 0.5 microgram/kg amylin was similar to that of 2.5 micrograms/kg amylin but the duration of the effect was somewhat shorter with the low dose. Amylin (1 microgram/kg, IP) had no influence on gastric emptying. In conclusion, the hypophagic effect of peripherally administered amylin does not depend on an intact abdominal vagus or on an indirect effect via gastric emptying. It may therefore be hypothesized that amylin has a central site of action.

Abdomen↗

PubMed1995

A Na(+)-dependent mechanism is involved in mucosal uptake of cinnamic acid across the jejunal brush border in rats.

Phenolic acids are present in all plant-derived foods and in most diets. Indirect evidence indicates substantial absorption of phenolic monomers from the gastrointestinal tract. However, the mechanisms involved in the absorptive process are unknown. The present study investigates mucosal uptake of radioactively labeled cinnamic acid as a model substance for monomeric cinnamic acid derivatives (e.g., cinnamic, ferulic or caffeic acid) in the rat jejunum using an in vitro mucosal uptake technique. The results indicate the existence of a Na(+)-dependent saturable transport mechanism for uptake of cinnamic acid across the jejunal brush border membrane. The observed Na+ dependence of jejunal cinnamate uptake seems not to be related to the activity of the Na+,H+ exchanger. Lowering the pH of the incubation medium resulted in a pronounced increase in mucosal cinnamate uptake that can be only partially explained by an increase in nonionic diffusion of cinnamic acid. Furthermore, jejunal uptake of cinnamate seems to be influenced by intracellular HCO3- and/or pH, since the addition of methazolamide to a HCO3(-)- and CO2-free incubation medium significantly inhibited mucosal cinnamate uptake, whereas methazolamide was without an effect in the presence of HCO3- and CO2 in the incubation medium. Unlabeled cinnamic and ferulic acid as well as short-chain fatty acids (acetic, propionic and butyric acid) significantly inhibited Na(+)-dependent uptake of radioactivity labeled cinnamic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Swelling-activated conductances for chloride, potassium and amino acids in the rat colon: a whole-cell study.

Cell swelling induced by superfusion with a hypotonic medium (152 mosmol l-1) induced a reversible membrane depolarization of 13.8 +/- 5.3 mV in isolated colonic crypts during whole-cell recording using nystatin-permeabilized patches. This depolarization was concomitant with an increase in Cl- current as shown by anion substitution. In the absence of Cl- ions, the effect of the hypotonic medium was reversed into a hyperpolarization, which was associated with an increase in membrane outward (K+) current. The hyperpolarization was dependent on the presence of Ca2+ ions. It was blocked by TMB-8 ((N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride; 10(-5) mol l-1), an inhibitor of intracellular Ca2+ release, but not by a Ca2+ channel blocker, verapamil (5 x 10(-5) mol l-1). Using butyrate as a stimulus for cell swelling, it was investigated whether swelling induces a conductance for an amino acid, glutamate. In the absence of Cl- ions, superfusion with butyrate induced a reversible depolarization when glutamate was present in the intracellular medium, and a reversible hyperpolarization when glutamate was present in the extracellular medium. This response was blocked by the lipoxygenase inhibitor, NDGA (nordihydroguaiaretic acid, 10(-5) mol l-1), and was markedly attenuated when glutamate was replaced by the poorly permeable anion, gluconate. Measurements of the membrane current during voltage clamping revealed a modest increase in membrane current carried by glutamate during cell swelling. These results demonstrate that the dominant effect of cell swelling in rat colonic crypts is an increase in Cl- conductance, a smaller increase in K+ conductance and a modest increase in conductance of amino acids, such as glutamate.

Adenosine Triphosphate↗