bluuebunny/crossref_metadata_2025 huggingface dataset:
Rat lingual lipase: factors affecting enzyme activity and secretion.
Authors: Hamosh M
Published: December 2017

The lingual serous glands of rat tongue secrete a potent lipase that acts in the stomach in which it initiates the digestion of dietary fat. The subcellular localization of the enzyme and factors affecting its activity and secretion were studied in adult male Sprague-Dawley rats. In a fraction rich in secretory granules, 42% of the lipase content of lingual serous glands was recovered after fractionation of homogenates of discontinuous gradients of urografin in 0.3 M sucrose. Lipase secretion was stimulated by isoprenaline: 2 h after isoprenaline administration, the lipase content of lingual serous glands was 73 +/- 5% lower than that of the control group. Accumulation of lipase began 8 h after the injection, reaching 57 +/- 7% of the initial level of the control group after 25 h. Bilateral resection of the glosso-pharyngeal nerves or bilateral sympathectomy led to a 40--50% decrease of enzyme activity in 7 days. Enzyme activity was markedly affected by the fat content of the diet. Feeding a high-fat diet (22% corn oil) for a period of 2 wk led to a 45% increase in the lipase content of lingual serous glands. The exponential rise in the lipase activity of the lingual serous glands immediately after birth could be related to the high-fat content of rat milk. The data suggest that the lingual serous glands are similar to other exocrine glands such as pancreas and parotid gland in the subcellular localization of secretory enzymes and mechanisms of enzyme secretion.
Development of the circadian rhythm of jejunal sucrase activity in the weanling rat.
Authors: Beam H E , Henning S J
Published: December 2017

In the adult rat, fed ad libitum, the activity of jejunal sucrase shows a diurnal rhythm with a peak during the dark period. Ontogenically, sucrase activity appears around the 16th postnatal day, then rises rapidly, and reaches adult levels by the 25th day. Our aim was to determine the developmental stage at which the diurnal rhythm appears and to elucidate its physiological basis. When sampled every 3 h on the 19th day, jejunal sucrase showed no discernible pattern with time. In contrast, at 22 days (1 day after completion of weaning) a circadian rhythm very similar to that of adults had appeared. Weights of stomach contents showed that the adult pattern of nocturnal feeding also matured between days 19 and 22. When weaning was prevented, no sucrase rhythm was detected on day 22, despite an imposed rhythm of suckling. Thus the sucrase rhythm is normally cued by some aspect of weaning other than rhythmic ingestion per se. Although corticosterone seemed a likely mediator of the sucrase rhythm, studies in adult rats showed that the rhythm persists in adrenalectomized animals.
Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.
Authors: Weitzman R E , Fisher D A
Published: December 2017

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.
Disruptive effect of test meals on interdigestive motor complex in dogs.
Authors: De Wever I , Eeckhout C , Vantrappen G , Hellemans J
Published: December 2017

The disruptive effect of food and food components on the migrating myoelectric complex (MMC) was studied in conscious dogs. Three types of test meals were fed, and the interval between feeding and the reappearance of the first phase III of the MMC was determined. When commercial dog food was used a linear relation was observed btween the quantity of food (expressed as kcal/kg body wt) and the duration of the disruption of the MMC. Equicaloric amounts of the three major food components disrupted the MMC pattern for periods of time that were related to the nature of the food: the effect of arachis oil lasted longer than that of sucrose and much longer than that of milk protein. Medium chain triglycerides had a potent disruptive effect. Mixtures of these food components produced a disruptive effect that could not be calculated from the individual effect of each component. Phase III of the first and second MMC after feeding started at a lower level of the intestine than after a long fast. The duration of disruption of the MMC after a meal depends much more on the physicochemical composition of the food than on its volume or amount of calories.
Kinetics of amylase release by dispersed acini prepared from guinea pig pancreas.
Authors: Peikin S R , Rottman A J , Batzri S , Gardner J D
Published: December 2017

When incubated with a secretagogue such as cholecystokinin (CCK), dispersed acini prepared from guinea pig pancreas released substantially more amylase than did dispersed single acinar cells. With CCK the rate of amylase release from dispersed acini decreased after 5 min of incubation and remained constant for the subsequent 25 min. The magnitude of the reduction in the rate of amylase release after 5 min was greater with higher concentrations of CCK. With vasoactive intestinal peptide (VIP), the rate of amylase release remained constant for at least 30 min. With CCK plus VIP, potentiation of the rate of amylase release occurred only during the first 15 min of incubation. After 15 min of incubation, the effects of the two peptides were additive. When dispersed acini were first incubated with CCK, potentiation of amylase release occurred only when VIP was added during the initial 10 min of incubation. In contrast, when cells were first incubated with VIP, potentiation of amylase release occurred when CCK was added as long as 30 min after VIP.
Unstirred water layer and age-dependent changes in rabbit jejunal D-glucose transport.
Authors: Thomson A B
Published: December 2017

The unidirectional flux of solutes into the intestinal mucosal cell is determined by passage through the microvillus membrane and the overlying unstirred water layer, UWL. An in vitro technique was employed to determine the effect of the UWL on glucose transport into the jejunum of suckling, mature, and old rabbits. When the resistance of UWL was high, the uptake from high concentrations of glucose increased as the animals grew older; this change with aging was not seen from low concentrations of glucose. When UWL resistance was minimized by stirring the bulk phase, similar amounts of glucose were absorbed from high doses, but uptake from low doses was greater in young than in old animals. Studies undertaken to determine the kinetic basis of these age-related changes showed that with increasing age i) the apparent passive permeability coefficient P of glucose fell, ii) the maximum transport rate Jdmax rose, and iii) the apparent affinity constant Km increased. These differences were not observed when the resistance of the UWL was high: P and Km were similar in suckling, mature, and old animals, and the increase in glucose uptake with age was due to the greater Jdmax. Thus the potential benefit of the high affinity, high permeability transport system of young animals may be obscured by high resistance of the UWL.
Stimulation and blockade of cholinergic receptors in terminal liver microcirculation in rats.
Authors: Koo A , Liang I Y
Published: December 2017

This study was designed to establish the existence of cholinergic vascular receptors in the terminal portion of the rat liver microcirculation. The liver microcirculation was observed in vivo by a transillumination technique through a television microscope. The changes in the caliber of the liver sinusoids were measured directly on the television screen. Infusion of the parasympathetic neurotransmitter acetylcholine into the portal venous circulation caused a concentration-dependent dilation of liver sinusoids. Similar dilatation effects were observed for other cholinergic receptor agonists. Atropine, the specific cholinergic receptor blocker, inhibited this dilator effect, displacing the acetylcholine concentration-effect curve to the right. In contrast, physostigmine, the cholinesterase inhibitor, caused displacement of the curve to the left. In conclusion, cholinergic receptors are present in the terminal portion of the liver microcirculation, subserving the functional role of vasodilatation.
Stimulation of iron absorption by polychlorinated aromatic hydrocarbons.
Authors: Manis J , Kim G
Published: December 2017

Oral and intraperitoneal treatment of rats with a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 33 microgram/kg, causes a 41--67% increase in iron adsorption in vivo. The major effect is on the transfer of iron from the mucosa into the bloodstream rather than on the uptake of iron from the lumen of the gut. These results are confirmed in studies with everted gut sacs. The effect is maximal at 1--2 days with a dose of 22-42 microgram/kg. Calcium transport is inhibited by TCDD treatment, whereas galactose and proline transport are unaffected. Treatment of rats with 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane also stimulates iron transport. Concomitant with iron transport stimulation, aryl hydrocarbon hydroxylase activity in the intestine and liver is increased by TCDD treatment. These studies suggest that polychlorinated aromatic hydrocarbons, which are environmental health hazards, may effect the intestinal absorption of essential mineral nutrients.
Sequential insulin degradation in cultured fetal hepatocytes in relation to chloroquine-dependent events
Authors: Zachayus J. L. , Khan S. , Plas C.
Published: December 2017

Insulin cellular degradation was studied in cultured 18-day-old fetal rat hepatocytes in the presence and absence of insulin degradation inhibitors that decrease the glycogenic response to insulin. After cell incubation with 3 nM [125I]A14 or -B26 insulin, hormone degradation products associated with cells or present in the medium were analyzed by high-performance liquid chromatography. Within cells, four components containing intact [125I]A14 insulin A-chain and part of the B-chain (A1-A4, according to increasing retention times) were found together with two [125I]B26 insulin B-chain COOH-terminal fragments (B1 and B2). Medium degradation intermediates comprised B1 and B2 but not A1-A4. Cellular insulin fragments A3 and B2 exhibited a maximal transient accumulation after 2 min, whereas the others increased progressively to plateau after 10 min. Chloroquine inhibited the formation of A1, A2, and B1 by 70-80%, whereas that of A3, A4, and B2 was not significantly affected. N-ethylmaleimide and bacitracin, two inhibitors of insulin-degrading enzyme (IDE), decreased the formation of chloroquine-dependent cellular peptides. Thus cell-associated insulin degradation implied primarily two cleavages in B-chain near the COOH-terminus, the one sensitive to chloroquine and IDE inhibitors occurring after endosomal segregation of insulin and its receptor.
Euglycemic hyperinsulinemia and hyperaminoacidemia decrease skeletal muscle ubiquitin mRNA in goats
Authors: Larbaud D. , Debras E. , Taillandier D. , Samuels S. E. , Temparis S. , Champredon C. , Grizard J. , Attaix D.
Published: December 2017

Insulin inhibits protein breakdown at the whole body level, but neither the tissues nor the proteolytic pathways on which insulin exerts its antiproteolytic effect are well characterized. We measured the effects of insulin on mRNA levels for cathepsin D and m-calpain (a lysosomal and Ca2(+)-dependent proteinase, respectively) and ubiquitin (a component of ubiquitin-dependent proteolysis) in skeletal muscle, skin, liver, and intestine. We used a 6-h hyperinsulinemic, euglycemic, and hyperaminoacidemic clamp in goats, a species in which insulin markedly inhibited whole body protein breakdown under similar conditions [S. Tesseraud, J. Grizard, E. Debras, I. Papet, Y. Bonnet, G. Bayle, and C. Champredon. Am. J. Physiol. 265 (Endocrinol. Metab. 28): E402-E413, 1993]. Hyperinsulinemia and hyperaminoacidemia had no effect on cathepsin D, m-calpain, and ubiquitin mRNA levels in liver, skin, and jejunum. In contrast, depressed ubiquitin mRNA levels were seen in skeletal muscle without any concomitant reduction in mRNA levels for cathepsin D, m-calpain, and other components of the ubiquitin-dependent proteolytic pathway. The reduced ubiquitin mRNA levels in skeletal muscle may represent a possible mechanism explaining the antiproteolytic effect of insulin in vivo.
Regulation of peptide-chain initiation in muscle during sepsis by interleukin-1 receptor antagonist
Authors: Vary T. C. , Voisin L. , Cooney R. N.
Published: December 2017

The mechanism by which interleukin-1 (IL-1) regulates protein synthesis in skeletal muscle during hypermetabolic sepsis in rats was investigated. Treatment of septic rats with a specific interleukin-1 receptor antagonist (IL-1ra) prevented the sepsis-induced inhibition of protein synthesis and translational efficiency in gastrocnemius. Analysis of ribosomal subunits revealed that the increase in free 40S and 60S ribosomal subunits observed in septic rats was prevented by infusion of IL-1ra, indicating peptide-chain initiation was maintained at control values. The failure of sepsis to inhibit peptide-chain initiation after infusion of IL-1ra correlated with a maintenance of the epsilon-subunit of eukaryotic initiation factor (eIF) 2B (eIF-2B epsilon) protein at control values. The alterations in the eIF-2B epsilon protein content in gastrocnemius of septic rats treated with or without IL-1ra were associated with corresponding changes in the abundance of eIF 2B epsilon mRNA. The results provide evidence that infusion of IL-1ra attenuates the sepsis-induced inhibition of protein synthesis by preventing the inhibition of peptide-chain initiation and downregulation of eIF-2B expression during sepsis.
Regulation of lipid metabolism in adipose tissue during early starvation
Authors: Samra J. S. , Clark M. L. , Humphreys S. M. , Macdonald I. A. , Frayn K. N.
Published: December 2017

We studied changes in lipid metabolism in adipose tissue in 24 healthy adults during early starvation (14-20 h) by cannulating the venous drainage of the subcutaneous adipose tissue of the anterior abdominal wall. Net nonesterified fatty acid (NEFA) efflux from adipose tissue increased steadily from 1,790 +/- 300 to 2,360 +/- 290 nmol.100 g-1.min-1 (P = 0.03), due to increasing transcapillary efflux of NEFA (release from adipocytes; P < 0.01). The reesterification rate after an overnight fast was close to zero; thus, reduction in the rate of reesterification played no part in the increased transcapillary efflux of NEFA. One-quarter of the net efflux of NEFA after an overnight fast arose from the action of lipoprotein lipase (LPL), although this relative contribution decreased during the study (P < 0.02). The increased transcapillary efflux of NEFA reflected a significant increase in the rate of action of hormone-sensitive lipase (HSL; P = 0.03). There was a strong relationship between mean arterial NEFA concentration and net NEFA release from adipose tissue (P < 0.001), implying that the particular depot studied reflects the behavior of adipose tissue as a whole. Thus the increasing efflux of NEFA from adipose tissue observed during early starvation is due to an increased rate of action of HSL, which may in turn be regulated by a fall in the plasma insulin concentration.
Characterization of bombesin effects on canine gastric muscle
Authors: Mayer E. A. , Elashoff J. , Walsh J. H.
Published: December 2017

Synthetic bombesin increased the frequency and amplitude of spontaneously occurring contractions of muscle strips from antrum and corpus of the canine stomach in vitro. The effect of bombesin on frequency of contractions in this system was myogenic; was unrelated to receptors for acetylcholine, norepinephrine, substance P, or cholecystokinin; and was independent of extracellular calcium. The effect of bombesin on the amplitude in the circular muscle was unaffected by tetrodotoxin and atropine but locked by verapamil, whereas in the longitudinal muscle it was blocked by tetrodotoxin and atropine. In the circular antral muscle bombesin was approximately 100,000 times more potent than acetylcholine at threshold concentrations and was equipotent to cholecystokinin. The high potency of bombesin and its known presence in gastric nerve fibers make it a candidate for a neurotransmitter function in regulation of gastric mobility.
Hormonal effects on the pylorus
Authors: Phaosawasdi K. , Fisher R. S.
Published: December 2017

The control mechanisms of pyloric pressure responses have not been elucidated clearly. The purposes of this study were twofold: 1) to determine the dose-related pressure responses of the pylorus to exogenous glucagon, secretin, and cholecystokinin, and 2) to correlate changes in pyloric pressure with serum concentrations of these hormones. Pyloric pressures were measured by infusion manometry, and the serum concentrations of glucagon and secretin were quantitated using radioimmunoassays. Each of the hormones tested, glucagon, secretin, and cholecystokinin, increased the pyloric pressure significantly. The lowest active dosages tested for each of these peptide hormones were 2 micrograms.kg-1.h-1, 2 U.kg-1.h-1, and 1 U.kg-1.h-1, respectively. The maximal pyloric pressure responses recorded were 8.7 +/- 1.1 (P less than 0.05), 12.6 +/- 2.1 (P less than 0.02), and 14.8 +/- 1.7 (P less than 0.02) mmHg, respectively. The pyloric pressure responses to insulin hypoglycemia, duodenal acidification, and intraduodenal olive oil were 11.3 +/- 1.5, 13.4 +/- 1.4, and 11.3 +/- 1.4 mmHg, respectively. The serum concentrations of immunoreactive glucagon during infusion of the lowest active dosage of glucagon and insulin hypoglycemia were 801 +/- 55 and 322 +/- 12 pg/ml, respectively. The serum concentrations of immunoreactive secretin during infusion of the lowest active dosage of secretin and during duodenal acidification were 980 +/- 60 and 110 +/- 7.0 pg/ml, respectively. Although pyloric contraction can be induced by administration of exogenous glucagon, secretin, and cholecystokinin, these studies suggest that these effects may have no physiological relevance.
Bile acid transport in cultured rat hepatocytes
Authors: Van Dyke R. W. , Stephens J. E. , Scharschmidt B. F.
Published: December 2017

The mechanisms of bile acid uptake have been studied with primary monolayer cultures of rat hepatocytes. Hepatocytes were incubated with taurocholic acid (TC), glycocholic acid (GC), cholic acid (CA), glycochenodeoxycholic acid (GCDC), chenodeoxycholic acid (CDCA), deoxycholic acid (DOCA), lithocholic acid (LCA), or cholylglycylhistamine (CCH), a neutral bile acid derivative for 10 s to 60 min in medium containing sodium chloride, sodium chloride with 1 mM ouabain, or choline chloride. Cells were washed free of radioactive tracer, cell-associated radioactivity was quantitated, and bile acid uptake rates, kinetic parameters of uptake, and steady-state bile acid content were calculated. Two mechanisms for bile acid uptake were identified. Uptake of TC, GC, CA, and GCDC occurred predominantly via a sodium-dependent, ouabain-suppressible saturable mechanism, presumably sodium-coupled transport. Estimates of apparent Km and Vmax for these bile acids were TC, 33 micro M and 0.36 nmol . min-1 . mg prot-1; GC, 18 micro M and 0.22 nmol . min-1 . mg prot-1; CA, 13 micro M and 0.10 nmol . min-1 . mg prot; and GCDC, 6 micro M and 0.21 nmol . min-1 . mg prot, respectively. Uptake via this sodium-coupled mechanism exhibited considerable substrate selectivity. It was enhanced by increased ring hydroxylation and amino acid conjugation and decreased by further conjugation with a neutral histamine group (CGH). In contrast, uptake of CDCA, DOCA, LCA, and CGH occurred primarily via a nonsaturable sodium-independent mechanism, possibly simple diffusion. This mechanism accounted for only a small portion of uptake of TC, GC, CA, and GCDC at low bile acid concentrations. Nonsaturable bile acid uptake rates appeared to correlate with decane-buffer partition coefficients and to be related to bile acid structure.
Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension
Authors: Vorobioff J. , Bredfeldt J. E. , Groszmann R. J.
Published: December 2017

Two dissimilar hemodynamic hypotheses, the “backward flow” theory and the “forward flow” theory, have been advanced to define splanchnic hemodynamics in portal hypertension. An animal model with portal hypertension and high-grade portal-systemic shunting, the portal vein-stenotic rat, was studied to determine whether a hemodynamic picture compatible with either theory would develop. Splanchnic and systemic hemodynamics and portal-systemic shunting were measured by radioactive microsphere techniques. The portal-hypertensive rats (portal pressure, 12.8 +/- 0.5 vs. 8.3 +/- 0.4 mmHg) with greater than 95% portal-systemic shunting had a 60% increase in portal venous inflow (23.46 +/- 2.54 vs. 14.97 +/- 1.61 ml/min; P less than 0.01) with a concomitant 50% decrease in splanchnic arteriolar resistance (3.86 +/- 0.43 vs. 7.60 +/- 0.80 dyn . s . cm-5 . 10(5); P less than 0.001) compared with control rats. Cardiac index (391 +/- 17 vs. 250 +/- 20 ml . min-1 . kg-1) was elevated 50% (P less than 0.001), and total peripheral resistance (7.1 +/- 0.4 vs. 11.7 +/- 0.8 dyn . s . cm-5 . 10(4)) was decreased 60% (P less than 0.001). The resistance to portal blood flow in portal vein-stenotic rats (4.77 +/- 0.57 dyn . s . cm-5 . 10(4)) was similar to the resistance to portal blood flow in control rats (4.82 +/- 0.43 dyn . s . cm-5 . 10(4)), indicating that the hyperdynamic portal venous inflow, not resistance, provided the main impetus for maintaining the elevated portal venous pressure. The splanchnic hemodynamic observations directly support the forward flow theory of portal hypertension. The relation between splanchnic arteriolar resistance and total peripheral resistance (r = 0.67; P less than 0.01) indicated that the systemic hemodynamic parameters were secondarily altered by the splanchnic hemodynamic changes. This animal model of chronic portal hypertension gave evidence for a generalized splanchnic arteriolar vasodilation occurring in the presence of high-grade portal-systemic shunting.
Hepatic uptake of albumin-bound substances: albumin receptor concept
Authors: Ockner R. K. , Weisiger R. A. , Gollan J. L.
Published: December 2017

The single-pass hepatic uptake of long-chain fatty acids and other substances bound tightly to albumin in plasma is surprisingly efficient. Recent kinetic studies for several of these substances suggest that uptake is mediated primarily by direct interaction of the albumin-ligand complex with the hepatocyte surface rather than by the small fraction of unbound ligand, as has been generally believed. Furthermore, 125I-albumin has been found to bind specifically, saturably, and reversibly to isolated hepatocytes, adipocytes, and erythrocytes. Although the nature and possible regulation of these binding sites remain to be fully elucidated, the putative albumin receptor may play an important role in the bidirectional transfer of many classes of endogenous and exogenous substances between albumin and cells.
Brain stem response to phasic gastric distension
Authors: Barber W. D. , Burks T. F.
Published: December 2017

To explore the physiological characteristics of central projections of gastric afferent fibers, single-unit activity was recorded extracellularly from neurons in the brain stem during phasic distension of the stomach in cats anesthetized by halothane and nitrous oxide. The brain stem units were identified on the basis of discharge patterns that were phase locked to distension or relaxation of the stomach. Based on stereotaxic coordinates, the units responding to the distension stimulus were located in the region of nucleus and tractus solitarius and extended ventrally toward nucleus ambiguus. Both phasically and tonically discharging units were identified, which exhibited either an excitatory or inhibitory response during distension of the stomach at pressures of 6-8 cmH2O. Units excited by distension increased their firing rate or began to discharge near the peak of distension at rates of 4-6 Hz. Other units responded only during the phase when the distending pressure was decreasing. Sectioning the vagi abolished the response of these brain stem units to gastric distension. The origin of the stimulus that initiated the unit response was localized in the fundus and body of the stomach in many instances. The results indicate that neuronal activity in discrete areas of the brain stem of the cat is altered in response to phasic gastric distension and that this response is vagally mediated.
Adaptive regulation of sugar and amino acid transport by vertebrate intestine
Authors: Karasov W. H. , Diamond J. M.
Published: December 2017

The adaptive regulation of sugar and amino acid transport by vertebrate intestine constitutes a neglected area. We review the patterns, signals, and mechanisms involved in adaptation. Mechanisms include changes in mucosal mass, specific transport systems, and the sodium gradient. Signals include the transported solutes themselves, hormones, and pancreaticobiliary secretions. The pattern of adaptation is examined for effects of dietary solutes, starvation, hyperphagia, dietary bulk, diabetes, intestinal position, intestinal resection, time of day, season of the year, hibernation, gestation, lactation, and aging and for differences among species. These observed patterns are compared with the patterns predicted by a simple teleologically deduced hypothesis: increased metabolic requirements should be met by increased absorption achieved through increased mucosal mass, while nutritionally essential solutes and nonessential solutes used as calorie sources should, respectively, repress and induce their own transport. We conclude with a summary of major unsolved questions in this area.
Taurocholate, but not taurodehydrocholate, increases biliary permeability to sucrose
Authors: Reichen J. , Le M.
Published: December 2017

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.
Bicarbonate sulfate exchange in canalicular rat liver plasma membrane vesicles
Authors: Meier P. J. , Valantinas J. , Hugentobler G. , Rahm I.
Published: December 2017

The mechanism(s) and driving forces for biliary excretion of sulfate were investigated in canalicular rat liver plasma membrane vesicles (cLPM). Incubation of cLPM vesicles in the presence of an inside-to-outside (in, out) bicarbonate gradient (50 mM in, 5 mM out, pH 8.0 in and out), but not pH (pH 8.0 in, 6.0 out) or out-to-in sodium gradients, stimulated sulfate uptake 10-fold compared with the absence of bicarbonate and approximately 2-fold above sulfate equilibrium ("overshoot"). Initial rates of this bicarbonate gradient-driven sulfate uptake were saturable with increasing concentrations of sulfate (apparent Km, approximately 0.3 mM) and could be inhibited by probenecid, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate, acetazolamide, furosemide,4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (IC50, approximately 40 microM). Cisinhibition of initial bicarbonate gradient-stimulated sulfate uptake and transstimulation of sulfate uptake in the absence of bicarbonate were observed with sulfate, thiosulfate, and oxalate but not with chloride, nitrate, phosphate, acetate, lactate, glutamate, aspartate, cholate, taurocholate, dehydrocholate, taurodehydrocholate, and reduced or oxidized glutathione. These findings indicate the presence of a sulfate (oxalate)-bicarbonate anion exchange system in canalicular rat liver plasma membranes. In conjunction with the previously reported chloride-bicarbonate exchanger (J. Clin. Invest. 75: 1256-1263, 1985), these findings support the concept that bicarbonate-sensitive transport system might play an important role in bile acid-independent canalicular bile formation.
Intestinal adaptations of rainbow trout to changes in dietary carbohydrate
Authors: Buddington R. K. , Hilton J. W.
Published: December 2017

Although omnivores are able to alter the structure and functions of their digestive system in response to changes in dietary carbohydrate content, it is unclear whether carnivores are capable of such adaptive flexibility. Hence we recorded growth rates, intestinal morphometrics and histology, and nutrient uptake rates and concentrations of disaccharidases in the intestines of a carnivorous fish, the rainbow trout, fed different levels and types of carbohydrate. The trout is unable to adaptively regulate digestive system structure and function to increase glucose availability in response to increasing levels of dietary carbohydrates, even to easily digestible forms such as glucose. Paradoxically, a reduction in the concentrations of enzymes associated with carbohydrate digestion in response to elevated levels of easily digested carbohydrates suggests that carnivores may actually try to repress carbohydrate digestion when glucose is available in high quantities. Thus the lower levels of carbohydrate in the diet of trout throughout their evolution has resulted in a reduced ability to phenotypically regulate the digestion of carbohydrates.
Mediators of anaphylaxis-induced ion transport changes in small intestine
Authors: Castro G. A. , Harari Y. , Russell D.
Published: December 2017

Net ion transport by jejunum of rats immunized against Trichinella spiralis on challenge with parasite-derived antigen was measured in Ussing chambers as a rapidly expressed, biphasic rise and fall (phase I and II) in short-circuit current (delta Isc). This delta Isc is triggered by mucosal anaphylaxis. Our objective is to identify mast cell-derived substances that mediate the epithelial response. Antigenic challenge of sensitized jejunum caused the release of 5-hydroxytryptamine (5-HT), histamine, and prostaglandin E2 (PGE2). The antigen-induced phase I response was mimicked by exogenous 5-HT or histamine and blocked by pretreatment of tissue with 5-HT and histamine H1-antagonists; the phase II response was mimicked by exogenous PGE2 and blocked by an inhibitor of prostaglandin synthesis. Atropine and tetrodotoxin significantly blunted the phase I response as well as the delta Isc caused by exogenous 5-HT or histamine while only slightly reducing the phase II response and not affecting the delta Isc induced by PGE2. Results support the conclusion that 5-HT, histamine, and PGE2 mediate the antigen-induced change in Isc through direct and neurally mediated stimulation of jejunal epithelium.
Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus
Authors: Wiley J. , Owyang C.
Published: December 2017

The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8-bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8-bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhancement of intestinal growth in neonatal rats by epidermal growth factor in milk
Authors: Berseth C. L.
Published: December 2017

Breast milk has been shown to enhance neonatal intestinal growth. Because epidermal growth factor (EGF) is present in the milk of various mammalian species, the hypothesis was tested that EGF in rodent milk mediates, in part, the breast milk-enhanced intestinal growth in neonatal rat. Fifty-eight rat pups fed artificial formula that contained 1.2, 3.0, and 6.0 micrograms/ml EGF for 39 h had greater incorporation of [3H]thymidine into DNA and DNA content of intestine than 29 pups fed unsupplemented formula. Pups fed EGF for 5 days had significantly greater body weight, intestinal weight, length, and DNA content than control pups. Conversely, pups fed pooled rat milk containing rabbit-derived antibody to EGF for 39 h had intestines of lower weight that contained less DNA than animals fed rat milk containing normal rabbit serum. EGF appears to mediate in part, breast milk-enhanced neonatal intestinal growth.
Contraction mediated by Ca2+ influx in esophageal muscle and by Ca2+ release in the LES
Authors: Biancani P. , Hillemeier C. , Bitar K. N. , Makhlouf G. M.
Published: December 2017

Single cells and whole tissue specimens were used in this study to determine sources of Ca2+ utilized for contraction of the circular muscle layer of esophagus and lower esophageal sphincter (LES) of the cat. In vitro circular muscle specimens from the cat esophagus respond to electrical stimulation with phasic contractions at the end of the stimulus, whereas the LES spontaneously maintains tonic contraction and relaxes during stimulation. In Ca2+-free buffer, esophageal contractions rapidly decline and disappear within 10 min after the removal of Ca2+, while LES tone is only partially reduced. Similarly, incubation in a solution containing the Ca2+ influx blocker, La3+, abolishes esophageal contraction but only partially decreases LES tone. Conversely, strontium and caffeine substantially reduce LES tone without affecting the amplitude of esophageal contractions. In single muscle cells isolated by enzymatic digestion from the LES and the body of the esophagus, blockade of extracellular Ca2+ influx by methoxyverapamil (D 600) or ethyleneglycol-bis-(beta-aminoethylether) N,N'-tetraacetic acid abolished esophageal contraction in response to acetylcholine without affecting LES cells, and conversely, strontium abolished LES contraction without affecting esophageal cells. These data are consistent with the view that extracellular Ca2+ is required to initiate esophageal phasic contraction, while the LES has the ability to utilize intracellular Ca2+ to maintain resting tone and to contract in response to acetylcholine.
Modulation of histamine release from canine fundic mucosal mast cells
Authors: Soll A. H. , Toomey M. , Culp D. , Shanahan F. , Beaven M. A.
Published: December 2017

To study the control of histamine release, we developed techniques for culturing fundic mucosal mast cells. After enzyme dispersion, enrichment by elutriation, and overnight suspension culture, mast cells accounted for 30% of the cells present. Histamine release into the medium, measured by radioenzymatic assay, was stimulated by the lectin concanavalin A (Con A). Ragweed antigen released histamine in antisera-sensitized cultures. Con A-induced histamine release was enhanced by adenosine, but adenosine alone was inactive. The relative potency of adenosine analogues was consistent with interaction at an adenosine A1-receptor site. The calcium ionophore A23187 (0.1-1 microM) also induced histamine release. Phorbol esters that activate protein kinase C, such as phorbol 12-myristate 13-acetate, did not release histamine but enhanced release when added to low concentrations of A23187. In contrast, inactive phorbols, such as 4 alpha-phorbol 12,13-didecanoate, failed to enhance A23187-induced release. Parallel studies with canine hepatic mast cells yielded comparable results. We conclude that canine fundic mast cells possess receptors for immunoglobulin E and adenosine. Our data are consistent with increases in cytosolic calcium and protein kinase C activation working synergistically to stimulate fundic mast cells.
Influence of hormones on glycogen and glucose metabolism in embryonic chick intestine
Authors: Black B. L.
Published: December 2017

Previous studies on the development of embryonic intestine in vitro have revealed a stimulation of epithelial differentiation by the hormones hydrocortisone (HC) and thyroxine (T4). To determine whether these hormones also influence epithelial metabolism, duodena from 14-day-old chicken embryos were cultured for 72 h in the absence of hormones (controls) or in the presence of 1 nM T4 or 1 microM HC. In control cultures, glycogen accumulated within the duodenal epithelium to the level found at 17 days in vivo. T4 reduced glycogen accumulation to 34% of control values, whereas HC increased epithelial glycogen content by 45%. These hormonal effects were due, in part, to modulation of glycogen degradation. In T4 cultures, glucose oxidation activities within the epithelial layer and submucosal tissue were 300 and 140% of control values, respectively, and glucose utilization (removal from the culture medium) was increased. HC significantly decreased both glucose oxidation activity within the submucosal tissue and glucose utilization. These results are consistent with the hypothesis that HC regulates the early phase of epithelial differentiation that is characterized by low metabolic rate and accumulation of energy stores, whereas T4 elicits the prehatching phase of differentiation that is correlated with an increase in metabolic rate and utilization of stored products.
Intestinal anaphylaxis: rapid changes in mucosal ion transport and morphology
Authors: Baron D. A. , Baird A. W. , Cuthbert A. W. , Margolius H. S.
Published: December 2017

Anaphylactic reactions can be elicited by beta-lactoglobulin (beta LG) in the isolated colonic and ileal mucosae of guinea pigs fed cow milk. We have shown that these tissues respond to antigen challenge with a rapid rise in short-circuit current (SCC) due to net chloride secretion in the colon and less well-characterized ion movements in the ileum. Here, tissues were characterized morphologically at or near the peak of the SCC response 2 min after antigen addition. These sensitized preparations, or naive tissues passively sensitized with immune sera and challenged with beta LG, showed numerous structural alterations that correlated significantly with the change in SCC. In the ileum, these changes included compound exocytosis of mucous granules from goblet cells of crypts but not of villi and a decrease in the intercellular space of the crypts. In contrast, colonic goblet cells of both crypts and luminal surface showed no evidence of secretion, but crypt architecture was reproducibly and characteristically altered. Thus antigen challenge of intestinal mucosa results in temporally related but diverse changes in morphology and ion transport.
Taurine transport by rat intestine
Authors: Barnard J. A. , Thaxter S. , Kikuchi K. , Ghishan F. K.
Published: December 2017

Rat intestinal transport of taurine was studied using jejunal brushborder membrane vesicles and everted jejunal sacs. Membrane vesicle experiments showed that the initial rate (at 10 s) of 10 microM taurine uptake was stimulated 3.5-fold by an inwardly directed Na+ gradient when compared with a K+ gradient. The Cl- salt of Na+ supported uptake to a significantly greater degree than did more (SCN-) or less (SO2-4) permeant salts. Na+-stimulated uptake at 1 min achieved a value 2.5 times greater than equilibrium ("overshoot"). When 10 s taurine uptake was determined over a range of taurine concentrations (10-1,000 microM) and plotted using the Woolf-Hofstee equation, a diffusive and carrier-mediated component was apparent. Half-maximal, carrier-mediated uptake occurred at 25 +/- 9 microM taurine (Km). An inside-negative, valinomycin-induced K+ diffusion potential stimulated 10-s taurine uptake when compared with voltage-clamped conditions (4.9 vs. 2.6 pmol/mg protein; P less than 0.05). Incubation with a structural analogue, hypotaurine, reduced 10-s taurine uptake by 89%. Uptake by everted jejunal sacs also demonstrated Na+ stimulation and inhibition by hypotaurine. These data confirm the existence of a high-affinity rat jejunal brush-border membrane-associated taurine transport mechanism that is electrogenic, stimulated by a Na+ gradient, and modified by external Cl-.
Lymphatic pathways and role of valves in lymph propulsion from small intestine
Authors: Unthank J. L. , Bohlen H. G.
Published: December 2017

The pathways through which lymph is propelled from the mucosal, submucosal, and muscle layer lymphatics of the small intestine, the interconnections between these layers, and the location of lymphatic valves within these layers were studied. Injections of fluid into a single lacteal or submucosal lymphatic of rats, rabbits, dogs, and cats spread in all directions through the submucosal lymphatics and into laceteals but did not enter the lymphatics of the muscle layer. Injections into muscle layer lymphatics also spread in all directions but in no case entered the submucosal lymphatics. The submucosal and muscle layer lymphatics join within the bowel wall near the mesenteric border to form collecting lymphatics characterized by valves and spontaneous contractions. These data indicate that lymphatics of the mucosa and submucosa form a syncytium independent of the muscle layer lymphatics and that few if any valves exist within these lymphatic networks. Cycling lacteal pressures were measured when intestinal motility was present but not when motility was abolished, suggesting that intestinal motility might have a role in lymph propulsion.
Electrotonic current spread in colonic smooth muscle
Authors: Huizinga J. D. , Chow E.
Published: December 2017

Current-induced changes in the membrane potential (electrotonic potentials) were measured intracellularly. The electrotonic potentials were seen to decay exponentially over many cells, suggesting electrotonic current spread. The characteristics of the electrotonic current spread were used to determine passive membrane properties of both circular and longitudinal muscle cells of human and dog colon. Electrotonic current spread was first determined along the long axes of the cells. The space constant of the circular muscle of human colon was 2.14 mm and that of the longitudinal muscle was 1.63 mm. The space constants for the dog colon were similar. The value for the time constant of dog colon circular muscle was 160 ms, whereas much higher time constants, averaging between 500 and 800 ms, were recorded from dog longitudinal muscle and both human colon muscle layers. These data suggest good electrotonic coupling in all tissues studied, along the long axes of the cells. They further suggest a relatively high membrane resistance and junctional resistance in the longitudinal muscle. Electrotonic coupling along the short axes of circular muscle cells, along the long axis of the colon, was studied in the dog. The space constant was 0.43 mm, suggesting a relatively high resistance to current flow along the short axes of the cells. In addition, along the short axes of the cells from the submucosa to the myenteric plexus side (i.e., in radial direction) a gradient was observed in resting membrane potential, slow-wave amplitude, and rate of rise of the slow-wave upstroke.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of ability of various substance P antagonists to inhibit action of bombesin
Authors: Jensen R. T. , Heinz-Erian P. , Mantey S. , Jones S. W. , Gardner J. D.
Published: December 2017

In the present study the ability of two classes of substance P (SP) antagonists to affect SP- and bombesin (Bn)-stimulated amylase release, as well as binding of 125I-Bolton-Hunter (BH)-SP and 125I-[Tyr4]Bn, was studied to determine their mechanism of action and the relationship between inhibition of the action of SP and the action of Bn. Four SP analogues ([D-Pro2,D-Phe7,D-Trp9]SP, [D-Pro2,D-Trp7,9]SP, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP, and [D-Arg1,D-Trp7,9,Leu11]SP) and two SP-(4-11) analogues ([D-Pro4,D-Trp7,9]SP-(4-11) and [D-Pro4,D-Trp7,9,10]SP-(4-11)] did not stimulate amylase release when present alone but inhibited SP- and Bn-stimulated amylase release. For each SP analogue, inhibition was specific for peptides that stimulate release by interacting with SP or Bn receptors, whereas both SP-(4-11) analogues also inhibited cholecystokinin-stimulated amylase release. Each SP analogue's inhibition of Bn-stimulated amylase release was reversible. Each analogue inhibited binding of 125I-BH-SP with the same potency as it inhibited SP-stimulated amylase release and 125I-[Tyr4]Bn binding with the same potency as it inhibited Bn-stimulated amylase. In contrast, SP itself or SP-(4-11) itself did not inhibit Bn-stimulated amylase release or binding of 125I-[Tyr4]Bn. The relative affinities of the analogues for interacting with Bn and SP receptors differed. None of the analogues increased the dissociation of bound 125I-BH-SP or 125I-[Tyr4]Bn.(ABSTRACT TRUNCATED AT 250 WORDS)