bluuebunny/crossref_metadata_2025 huggingface dataset:
Bethanechol prevents inhibition of gastric acid secretion by gastric inhibitory polypeptide
Authors: Soon-Shiong P. , Debas H. T. , Brown J. C.
Published: December 2017

Earlier studies of gastric inhibitory polypeptide (GIP) have shown that it is a powerful inhibitor of acid secretion in denervated gastric pouches. Other studies, however, have shown that it is a weak inhibitor in innervated stomach preparations. In this study we evaluated the inhibitory action of GIP in four dogs, each provided with both a vagally denervated (Heidenhain) pouch and a gastric fistula of the innervated stomach. The effect of intravenous infusion of pure porcine GIP (1 microgram X kg-1 X h-1) on pentagastrin dose response was studied with and without background infusion of bethanechol (25 micrograms X kg-1 X h-1). GIP powerfully inhibited pentagastrin-stimulated acid secretion from the Heidenhain pouch but not from the gastric fistula. The maximal inhibition was 76% for the Heidenhain pouch and 29% for the gastric fistula. Despite the attainment of high levels of circulating immunoreactive GIP (greater than 3,000 pg/ml) early after the onset of infusion of the peptide, inhibition occurred relatively late, suggesting that this action of GIP might be mediated by the release of some other substance(s). Background infusion of bethanechol totally abolished the inhibitory action of GIP in both the Heidenhain pouch and gastric fistula.
Active transport of lead-210 by everted segments of rat duodenum
Authors: Barton J. C.
Published: December 2017

Everted gut sacs prepared from rat duodenum can transfer 210Pb from mucosal to serosal surfaces against concentration gradients in vitro. The mechanism requires oxygen and is significantly inhibited by sodium azide, sodium iodoacetate, 2,4-dinitrophenol, sodium cyanide, and sodium fluoride. Lack of oxygen or the presence of metabolic inhibitors produced greater relative inhibition of net serosal transfer but greater absolute decrements of net mucosal uptake. Treatment of rats prior to sac preparation with either intravenous FeCl2 or endotoxin, or the addition of FeCl2 to the mucosal medium, selectively inhibited net serosal transfer. Net mucosal uptake and net serosal transfer were significantly negatively correlated with animal weight. Jejunal or ileal sacs did not actively transport 210Pb.
Metabolism of human isoamylases in the rabbit
Authors: Rosenblum J. L. , Niesen T. E. , Alpers D. H.
Published: December 2017

Human isoamylases were purified from pancreas and saliva with separation of salivary isoenzymes into glycosylated and nonglycosylated forms. After iodination, bolus injection of each purified isoamylase into conscious rabbits revealed biexponential disappearance from plasma. Glycosylated salivary amylase had a metabolic clearance (t 1/2 = 35 min) that was three to four times faster than nonglycosylated salivary (t 1/2 = 139 min) or pancreatic (t 1/2 = 111 min) amylase. In contrast to our previous studies on homologous (rabbit) isoamylases, human pancreatic isoamylase was excreted into urine as protein-bound radioactivity more readily than salivary isoamylase. No organ contained more than 18% of the injected dose of radioactivity except for a striking accumulation of radioactivity in the liver after injection of 125I-labeled glycosylated salivary amylase. We concluded that 1) human nonglycosylated salivary amylase and pancreatic amylase are cleared from the rabbit circulation at rates comparable with those reported for homologous isoamylases in the rabbit and baboon, 2) the rabbit kidney excretes human pancreatic amylase into urine more readily than human salivary isoamylases, and 3) with the notable exception of glycosylated salivary isoamylase, human isoamylases do not appear to be metabolized primarily by any single organ.
Alpha 1-adrenergic inhibition of protein synthesis in rat submandibular cells
Authors: Takuma T. , Kuyatt B. L. , Baum B. J.
Published: December 2017

The incorporation of [14C]leucine into protein in dispersed cells from rat submandibular gland was inhibited by epinephrine. The dose required for a half-maximal effect was approximately 10(-6) M. This sensitivity is similar to that of mucin and potassium secretion induced by epinephrine from these cells. The inhibitory effect of epinephrine was mediated by the activation of alpha 1-adrenergic receptors and was partially independent of extracellular calcium. The calcium ionophore A23187 also decreased protein synthesis in the presence and absence of extracellular calcium. Epinephrine diminished alpha-[14C]aminoisobutyric acid (AIB) influx, but the extent of altered AIB uptake was much less than the extent of decrease in protein synthesis. Analysis of newly synthesized protein by gel electrophoresis and autofluorography showed that epinephrine selectively inhibited the synthesis of specific submandibular proteins. In aggregate these results suggest that activation of alpha 1-adrenergic receptors in rat submandibular cells influences the regulation of protein synthesis by a mechanism that uses intracellular calcium.
Apoprotein C effect on triglyceride transport in tandem-perfused rat hind end and liver
Authors: Kortz W. J. , Nashold J. R. , Greenfield M. R. , Hilderman H. , Quarfordt S. H.
Published: December 2017

The metabolism of double-labeled triglyceride in a synthetic emulsion was defined in an in vitro perfusion system of rat hind end and liver described previously [Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G106-G112, 1983]. The metabolism of [3H]glycerol-[14C]triolein was defined in the absence of added apoproteins and with additions of human CII and both CII and CIII. Without apoprotein, a pronounced lipolysis of the triglyceride was recognized by high concentrations of radiolabeled glycerol and free fatty acid in the perfusate. The removal of an aliquot of hind-end venous effluent 5 min after adding the labeled triglyceride emulsion to the arterial inflow demonstrated a brisk lipolysis of the substrate when incubated outside the perfusion system. The addition of CII protein to the emulsion before its introduction into the tandem system eliminated perfusate lipolysis, both within the perfusion system and in incubations of aliquots withdrawn from the system. Intravascular lipolysis was not seen with triglyceride emulsions containing both CII and CIH or when an aliquot of hind-end venous effluent was incubated with triglycerides that had not been exposed to the perfusion system. The intravascular lipolysis observed for the [14C]triglyceride added to the tandem system without apoproteins was associated with relatively greater recoveries of 14C-fatty acyl in liver, fat, and muscle and relatively greater recoveries of 14CO2 than when CII alone or both CII and CIII were added with the triglyceride. The addition of CIII to CII in a 1:1 molar ratio increased the recovery of 14C-fatty acyl in muscle and the recovery as 14CO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular and flux relationships in canine ileum
Authors: Mailman D.
Published: December 2017

Blood flow and pressure in denerved ileum of anesthetized dogs were altered by occlusion of the mesenteric artery or vein or by infusion of intra-arterial sodium nitroprusside (0.015-1.5 mg/min). Unidirectional Na and H2O fluxes were measured and absorptive site blood flow was estimated from the clearance of tritiated H2O. Net Na and H2O absorptions were reduced by mesenteric venous or arterial occlusion. Net secretion occurred with mesenteric venous occlusion. Nitroprusside reduced net absorption only at an infusion rate of 0.15 mg/min. The absorptive Na and H2O fluxes were reduced by both mesenteric venous or arterial occlusion, with venous occlusion being more effective. Nitroprusside reduced the absorptive Na flux at an infusion rate of 0.15 mg/min but not the absorptive H2O flux. The secretory flux of Na was increased by mesenteric venous occlusion but reduced by arterial occlusion and not changed by nitroprusside infusion. The secretory H2O flux was decreased by moderate degrees of mesenteric venous occlusion but was unchanged at greater levels. Arterial occlusion decreased secretory H2O fluxes. Nitroprossude infusion increased secretory H2O fluxes at an infusion rate of 0.015 mg/min. The absorptive and secretory Na and H2O fluxes were significantly correlated with absorptive site blood flow plus estimated capillary pressure. Absorptive site blood flow was primarily responsible for changes in absorptive fluxes and estimated capillary pressure for changes in secretory fluxes. Absorptive site blood flow affected the secretory and absorptive fluxes of H2O more equally than the Na fluxes.(ABSTRACT TRUNCATED AT 250 WORDS)
Reversible effects of phenothiazines on frog gastric stimulation
Authors: Raphael N. , Ekblad E. B. , Machen T. E.
Published: December 2017

The calmodulin inhibitors trifluoperazine (TFP), chlorpromazine (CPZ), and promethazine (PZ) were tested for effects on stimulus-secretion coupling in in vitro bullfrog gastric mucosa. When added to histamine-stimulated tissues, the drugs caused H+ secretion to decrease and transepithelial resistance to increase over a 2-h time course. The potency sequence was TFP (IC50 = 40 microM) greater than CPZ (IC50 = 72 microM) congruent to PZ (IC50 = 72 microM). Anesthetics and other phenothiazines with weak anticalmodulin activity had no effect on secretory parameters. In the presence of histamine, further addition of isobutylmethylxanthine (IBMX, a phosphodiesterase inhibitor) plus dibutyryl cAMP (DBcAMP), IBMX alone, or forskolin (a specific activator of adenylate cyclase) to phenothiazine-inhibited tissues caused full resumption of secretory activity. If TFP (50 microM) was added before stimulation with histamine, the normal increases in tissue cAMP content (which occurs primarily in oxyntic cells), oxyntic cell apical membrane elaboration (morphometric analysis of electron micrographs), and H+ secretion were all blocked. Subsequent addition of IBMX or IBMX plus DBcAMP completely reversed the TFP effect. These results indicate that the histamine-sensitive adenylate cyclase may be the site of TFP inhibition and Ca2+-calmodulin regulation; since these drugs inhibited stimulation by DBcAMP plus IBMX, they may also be exerting additional effects distal to cAMP generation.
Pancreatic blood flow in the rat during enlargement, involution, and cholecystokinin treatment
Authors: Oates P. S. , Bruce N. W. , Morgan R. G.
Published: December 2017

We studied the effect of raw soya flour (RSF) given as a single gavage or for long-term periods on pancreatic blood flow. These effects were compared with the response to treatment with cholecystokinin (CCK) since it has been suggested that RSF feeding releases CCK. In acute experiments total pancreatic blood flow was significantly increased after infusion of CCK (60 Ivy dog units X kg-1 X h-1) and after gavage with preparations of RSF or heated soya flour (HSF). When expressed as flow per 100 g pancreatic weight, the greatest increase was seen after gavage with RSF. In separate chronic studies, total pancreatic blood flow was significantly increased in rats fed RSF for 4 wk compared with rats fed HSF, but because of pancreatic enlargement in rats fed RSF flow per 100 g pancreatic weight was similar in the two groups. When rats fed RSF for 4 wk were changed to standard rat cubes for 48 h before study, pancreatic blood flow (ml/min and ml X min-1 X 100 g pancreas-1) and total pancreatic DNA decreased significantly compared with rats fed RSF continuously. However, when CCK was infused intravenously during the 48-h period on cubes, pancreatic blood flow and DNA remained significantly increased and were not significantly different from values in rats fed RSF continuously. These results show that the effects of RSF feeding and CCK treatment on pancreatic growth and blood flow are similar and are consistent with the postulated role of CCK as the trophic hormone released by RSF feeding.
Role of humoral factors in the intestinal hyperemia associated with chronic portal hypertension
Authors: Benoit J. N. , Barrowman J. A. , Harper S. L. , Kvietys P. R. , Granger D. N.
Published: December 2017

The role of neural, metabolic, physical, and humoral factors in the intestinal hyperemia associated with chronic portal hypertension was examined by use of the rat portal vein stenosis model. Intestinal blood flow and splenic pulp pressure were increased, while systemic arterial pressure and total vascular resistance were reduced in portal vein-stenosed rats as compared with controls. The reduction in total vascular resistance was entirely due to a fall in precapillary resistance and was accompanied by an increase in intestinal capillary pressure, which exceeded that produced by acute portal pressure elevation to the same level. Arteriovenous shunting of 15-micron microspheres was four times higher in portal-hypertensive rats. Cross-perfusion of control intestinal preparations with arterial blood from portal-hypertensive rats produced a 30% increase in blood flow. Plasma glucagon levels in portal-hypertensive rats were three times higher than in controls. Intra-arterial infusion of glucagon (at a rate that achieved the concentration measured in portal-hypertensive animals) produced a 20% reduction in intestinal vascular resistance. The results of these studies indicate that humoral factors, including glucagon, are primarily responsible for the hyperemia associated with portal hypertension.
Neural and hormonal control of membrane conductance in the pig pancreatic acinar cell
Authors: Pearson G. T. , Flanagan P. M. , Petersen O. H.
Published: December 2017

Intracellular microelectrode recordings from superfused segments of pig pancreas have shown the resting acinar cell membrane potentials to range widely, with a mean value of -30.5 +/- 1.3 mV. Electrical field stimulation (FS) of the intrinsic pancreatic nerves induced frequency-dependent membrane hyperpolarization (10-15 mV) accompanied by a concomitant reduction in input resistance. Similar effects could be evoked by the superfusion or electroionophoresis of acetylcholine, amphibian or mammalian bombesin [gastrin-releasing peptide (GRP)], and pentagastrin. In normal Ca2+-containing solutions sustained secretagogue superfusion resulted in sustained hyperpolarization. In the absence of external Ca2+, similar stimulation caused only a transient hyperpolarizing response, with subsequent periods of secretagogue application having no effect. Atropine completely abolished the FS-evoked hyperpolarizations but had no effect on the responses evoked by bombesin, GRP, and pentagastrin. The present findings support the contention that neural and hormonal stimulation of the pig pancreas evokes Ca2+-dependent acinar cell hyperpolarization by causing a selective increase in membrane K+ permeability. A hypothesis is proposed that cellular K+ release through the opened conductance pathway promotes a K+-Na+-Cl- cotransport into the cell that serves a key function in the generation of acinar salt secretion.
Interaction of cholera toxin and Escherichia coli enterotoxin with isolated intestinal epithelial cells
Authors: Hyun C. S. , Kimmich G. A.
Published: December 2017

The interaction of biologically active 125I-labeled cholera toxin with isolated chick intestinal epithelial cells involves a large number (approx 1.7 10(6)/cell) of high-affinity (Kd = 8–9 X 10(-9) M) binding sites that belong to a single class. Binding of iodotoxin to the cells occurs rapidly, is half-maximal within 1 min, and is complete in 3–7 min (at 37 degrees C) depending on the toxin concentration. Toxin binding is saturable and includes only a small contribution from nonspecific sites. Ligand competition studies suggest that the isolated B subunit of choleragen (CT-B) behaves in an almost identical fashion to the holotoxin (CT), whereas the A subunit shows no detectable activity in competitive binding. Assays for cAMP indicate that neither that A nor the B subunits of CT contain any activity for increasing the level of intracellular cAMP. B subunit, when incubated with CT, inhibits CT-induced elevation of cAMP in a dose-dependent manner. Preincubation of 125I-CT with various concentrations of ganglioside GM1 also shows a dose-dependent inhibitory effect on the binding activity of the toxin. Pretreatment of CT with increasing concentrations of GM1 results in a progressive decrease in toxin-induced formation of cAMP. Escherichia coli heat-labile enterotoxin, which is known to alter intestinal function via a mechanism similar to that of CT, has binding and biological effects very similar to thoseof CT.
Differential growth rate of rat gastric mucosal cells during postnatal ontogeny
Authors: Jacobs D. M. , Ackerman S. H.
Published: December 2017

The growth rate of surface epithelial, chief, and parietal cells of the base and neck of oxyntic glands was studied in the albino rat by comparing morphometric measures at days 15, 21, 30, and 100 postnatally. All cells increased in size. The number of cells per micrometer squared increased rapidly for chief cells and base parietal cells, while neck parietal cells remained constant and surface epithelial cells decreased. There was a net increase in the volume density of parietal and chief cells and a slight net decrease in surface epithelial cells during postnatal development. In a second experiment, the effects of early weaning on these variables was studied. Early-weaned rats gained less body weight than normally weaned counterparts. The change in surface epithelial cell size was not affected by early weaning. However, parietal and chief cells grew more quickly, initially, in early-weaned rats than in normally weaned rats. Cell numbers were unaffected except for an initial decrease in relative number of neck parietal cells. One long-term effect of early weaning was noted. The size and volume density of neck parietal cells in early-weaned rats was smaller, in the adult animal, then in normally weaned rats.
Modulation of gallbladder motility by intrinsic cholinergic neurons
Authors: Yau W. M. , Youther M. L.
Published: December 2017

The mechanical contraction and release of acetylcholine (ACh) were investigated by use of an isolated guinea pig gallbladder preparation subjected to transmural field stimulation. An increase in contraction amplitude was found to be related to the frequency (5-60 Hz) of applied stimulus. Treatment with tetrodotoxin and atropine prevented these electrically induced contractions. A simultaneous increase in the release of ACh was noted with electrical stimulation or depolarization by veratrine hydrochloride, and this increase was susceptible to blockade by tetrodotoxin. Neither contractions nor ACh release could be detected with stimulation at 0.1 Hz. When field stimulation was applied to contracted gallbladder induced by a supramaximal concentration of cholecystokinin octapeptide (CCK-8), a further increase in muscle tone was observed. The magnitude of this increase was frequency dependent. Although the onset of response to field transmural stimulation was relatively more rapid, the maximal response attained was only 70% of that elicited by CCK-8. When tissues were exposed to 2.2 X 10(-6) M CCK-8, the muscle contracted maximally but there was no increase in the efflux of [3H]ACh. These data provide a pharmacological characterization of the intrinsic gallbladder cholinergic neurons and demonstrate a possible role they may play in the control of gallbladder motility.
Regulation of intestinal goblet cell secretion. IV. Electrical field stimulation in vitro
Authors: Phillips T. E. , Phillips T. H. , Neutra M. R.
Published: December 2017

To determine whether transmitters released from enteric neurons can elicit secretion from goblet cells, full-thickness sheets of adult rat distal ileum or descending colon were mounted in modified Ussing chambers, and mucus secretion was assessed morphologically after electrical field stimulation (EFS). Square-wave pulses (56 V, 2 ms duration) were delivered at 10 Hz for 5 min. Goblet cells in colonic crypts, but not those on the mucosal surface, secreted mucus in response to EFS. This secretion was at least in part atropine insensitive, indicating a noncholinergic mechanism. In the ileum goblet cells located in the crypts, but not on villi, secreted mucus when tissue was mounted in the chamber, even in the absence of EFS. This “unelicited” secretion did not occur in unmounted control tissue in vitro, and it could be prevented by preincubating ileal tissue in 1 microM tetrodotoxin (TTX) or 10 microM atropine for 15 min before mounting. Furthermore, following preincubation with either TTX or atropine, EFS' failed to elicit secretion. Incubation of unmounted tissue with TTX, however, did not block the secretory response of crypt goblet cells to 20 microM carbachol. Thus, intrinsic cholinergic neurons may be sxtimulated during the mounting of the ileum in the chamber. Taken together, these data demonstrate that mucus secretion from crypt goblet cells may be regulated by cholinergic (in ileum and perhaps colon) and noncholinergic (in colon) elements of the enteric nervous system.
Gastrin receptors on nonparietal cells isolated from canine fundic mucosa
Authors: Soll A. H. , Amirian D. A. , Thomas L. P. , Park J. , Elashoff J. D. , Beaven M. A. , Yamada T.
Published: December 2017

The cellular localization of gastrin receptors was studied using dispersed canine fundic mucosal cells. In previous studies 125I-[Leu15]gastrin-17 (125I-[Leu15]G-17) binding was found to parietal cells, but gastrin binding was also found in the small-cell elutriator fractions (SCEF). In the present study a density gradient was used to further separate the SCEF and the distribution of 125I-[Leu15]G-17 binding correlated with cellular content of somatostatinlike immunoreactivity (SLI). In contrast, 125I-[Leu15]G-17 binding was inversely correlated with the histamine content of the fractions. 125I-[Leu15]G-17 binding to the SCEF was rapid and reversible. Total binding was 0.29 +/- 0.02 fmol/10(6) cells (mean +/- SE, n = 15); excess unlabeled G-17 inhibited 85% of this binding. G-17, [Leu15]G-17, and 127I-[Leu15]G-17 were equipotent in inhibiting 125I-[Leu15]G-17 binding and stimulating SLI secretion from the SCEF placed in short-term culture, whereas 127I-G-17 had a low potency for both effects. Proglumide, known to inhibit cholecystokinin binding to pancreatic acinar cell receptors, also inhibited 125I-[Leu15]G-17 binding to the SCEF and inhibited G-17 stimulated SLI release. We conclude that in the canine fundic mucosa gastrin interacts with receptor sites on parietal cells and somatostatin cells but probably not on fundic mucosal histamine-containing cells. These receptor sites for gastrin may activate counterbalancing mechanisms regulating the secretion of acid.
Alterations in motor function of the small intestine from intravenous and intraluminal cholecystokinin
Authors: Sninsky C. A. , Wolfe M. M. , McGuigan J. E. , Mathias J. R.
Published: December 2017

Cholecystokinin has been found within the lumen of the gastrointestinal tract; however, its effect on intestinal motility has not been studied. We examined the effect of intraluminal and intravenous infusion of the octapeptide of cholecystokinin (CCK-OP) on myoelectric activity in the intestine of rabbits. CCK-OP was infused intraluminally at 1,000 ng X kg-1 X h-1, and portal venous blood samples were obtained hourly for plasma immunoreactive CCK. CCK-OP was also infused intravenously at a similar rate, and hourly peripheral venous blood samples were obtained for plasma immunoreactive CCK. Myoelectric activity was monitored in a 12-cm ligated ileal segment and the proximal adjacent small intestine after the infusion of intraluminal or intravenous CCK-OP. Intraluminal infusion of CCK-OP caused a significant increase (P less than 0.01) in both migrating action potential complexes (MAPC) and repetitive bursts of action potentials (RBAP) (3.1 +/- 0.8 MAPC/h and 4.6 +/- 1.3 RBAP/h). In contrast, intravenous CCK-OP induced only repetitive bursts of action potentials (8.3 +/- 1.7 RBAP/h, P less than 0.01). In summary, alterations in intestinal motility may vary according to the route of administration of the individual peptide. Furthermore, results from these studies suggest that intraluminal release of regulatory peptides may be important in the modulation of intestinal motility.
Relation between dietary-induced increase of intestinal lactase activity and lactose digestion and absorption in adult rats
Authors: Leichter J. , Goda T. , Bhandari S. D. , Bustamante S. , Koldovsky O.
Published: December 2017

To study the relation between dietary-induced increase of intestinal lactase activity and lactose absorption, 11-wk-old rats were fed either a high-starch (70 cal%), low-fat (7 cal%) diet or a low-starch (5 cal%), high-fat (73 cal%) diet for 7 days. Food intake and body weight changes were similar in the two dietary groups. In the first experiment, lactose absorption was studied in vivo after oral administration of 600 mg lactose (10% solution in water with added [3H]PEG) to rats fasted for 16 h. Groups of rats were killed at time 0 and at 1-h intervals for the next 3 h. Lactase activity and lactose absorption were significantly higher (P less than 0.01) in the high-starch group than in the low-starch group. In the subsequent experiment, 9-wk-old rats were fed the two isocaloric diets for 3 days. By use of the everted sac technique, we have demonstrated a significantly higher absorption of monosaccharides from lactose in the high-starch diet group; also, glucose transport was higher in the high-starch diet-fed animals. When Tris, an inhibitor of lactase, was added into the mucosal fluid, absorption of lactose was abolished and no effect was seen on glucose absorption (in vivo and in vitro). In both experiments, significant linear regression was established between lactase activity and lactose absorption. Our results thus show that the increase in lactase activity, induced by feeding a high-starch diet to adult rats, is accompanied by an increased capacity to hydrolyze lactose and absorb the constituent monosaccharides.
Apical membrane properties and amiloride binding kinetics of the human descending colon
Authors: Wills N. K. , Alles W. P. , Sandle G. I. , Binder H. J.
Published: December 2017

The apical membrane properties of the isolated human descending colon were characterized by use of current fluctuation analysis methods and microelectrode techniques. The Na+ channel blocker amiloride was used to evaluate apical membrane conductance and the transepithelial short-circuit current (Isc). Amiloride significantly reduced Isc and increased the membrane resistance ratio. At submaximal doses of amiloride in the mucosal bathing solution, fluctuation analysis of the Isc revealed a Lorentzian component in the power-density spectra. The dose-response relationship between amiloride and current noise parameters was consistent with a two-state mechanism of blocker interaction with the channel. The on and off rate constants for the blocker-receptor reactions, the single-channel currents, and the Na+ channel densitywere estimated and were similar to those from Na+ channels from other so-called tight epithelia. In addition, these studies revealed an amiloride-insensitive conductance in the apical membrane in parallel to the amiloride-blockable Na+ channels. This conductance may be due to potassium ions. If so, the apical membrane properties of the human descending colon may closely resemble those of the rabbit descending colon and rat distal colon.
Effect of acid-base balance and acetazolamide on ursodeoxycholate-induced biliary bicarbonate secretion
Authors: Garcia-Marin J. J. , Dumont M. , Corbic M. , de Couet G. , Erlinger S.
Published: December 2017

Biliary bicarbonate secretion may play an important role in canalicular bile flow. The aim of this study was to examine the effect of disturbances in acid-base balance on ursodeoxycholate (UDCA)-induced choleresis and bicarbonate secretion. Isolated rat livers were perfused with an erythrocyte-free solution in a recirculating system. In the absence of bile acid infusion, bicarbonate concentration in bile varied in parallel with that in the perfusate (15.6-35.1 mM), irrespective of the perfusate pH (7.26-7.55). Bicarbonate concentration in bile was not significantly different from that in the perfusate. Under UDCA infusion (2 mumol/min), bicarbonate concentration in bile and perfusate was correlated (P less than 0.001). Bicarbonate concentration in bile was always higher than that in the perfusate. Perfusate pH changes (7.25-7.56) induced by changes in perfusate carbon dioxide tension had no significant effect on bicarbonate secretion or bile flow. A significant correlation was found between bile flow and bicarbonate secretion both with and without UDCA. Acetazolamide (1 mM) significantly decreased both UDCA-stimulated bile flow (-27.7%) and bicarbonate concentration (-51.8%). These results suggest that canalicular bicarbonate secretion includes an equilibrative component that is possibly linked to diffusion of plasmatic CO2 or HCO3- and a concentrative transport that is stimulated by UDCA, is independent of plasma pH, and involves carbonic anhydrase.
Colonic glycoprotein secretion and calmodulin-acceptor proteins in the reserpine-treated rat
Authors: Brady R. C. , Karnaky K. J. , Dedman J. R.
Published: December 2017

The rate of radioactive precursor-labeled colonic glycoprotein secretion in chronically reserpine-treated versus saline-injected control rats was examined. Everted colonic sacs prepared from reserpine-treated rats were found to be hypersecretory, exhibiting a basal rate of glycoprotein secretion that was threefold higher than control everted sacs. Furthermore, glycoprotein secretion in control tissue was stimulated by the secretagogue carbachol, and this stimulation was precluded by 10 microM trifluoperazine, the calmodulin antagonist. Reserpine-treated tissue, in contrast, was refractory to treatment with carbachol as well as trifluoperazine. While reserpine-treated and control colonic mucosae were demonstrated to contain equivalent levels of calmodulin via radioimmunoassay, reserpine-treated tissue was determined to lack two calmodulin-acceptor proteins with molecular weights of 29 and 47 kilodaltons. The data suggest that the mechanism by which reserpine elicits this cystic fibrosislike, hypersecretory state of glycoprotein secretion within the colonic mucosa entails the loss of calmodulin function in the regulation of this secretory process. We speculate that the biochemical defect present in cystic fibrosis could also entail such a loss of calmodulin function in the regulation of glycoprotein secretion.
Relation between pancreatic growth and blood flow
Authors: Harper S. L. , Granger D. N. , Barrowman J. A. , Kvietys P. R. , Ulrich M. G.
Published: December 2017

Male rats were treated with daily subcutaneous injections (3 micrograms/kg) of cholecystokinin octapeptide (CCK-OP), a synthetic CCK analogue, for 2, 4, 7, and 14 days, while control rats were injected with saline over the same intervals. Regional blood flows were measured with Sc46-labeled microspheres using the reference-organ method. Pancreatic wet and dry weights were determined in each treatment group. Total pancreatic DNA content was estimated with the diphenylamine reaction. Significant hyperplasia and increases in pancreatic wet weight occurred at 7 and 14 days, although hypertrophy was not evident in any of the treatment groups. No increases in small intestine wet weight or DNA content were evident in any treatment group. CCK-OP treatment induced a significant pancreatic hyperemia at 2 and 4 days of treatment. Pancreatic blood flow at 7 and 14 days was not different from control when expressed per unit tissue weight. The hyperemia seen at 2 and 4 days was not due to either a direct vascular effect of CCK-OP or an increase in pancreatic exocrine secretion. The hyperemia is therefore due to the growth stimulus and may be related to vasodilator metabolite accumulation during pancreatic tissue proliferation.
Vasoactive intestinal peptide as a neural mediator of gastric relaxation
Authors: Grider J. R. , Cable M. B. , Said S. I. , Makhlouf G. M.
Published: December 2017

Two main candidates, adenosine 5'-triphosphate (ATP) and vasoactive intestinal peptide (VIP), have been proposed as inhibitory transmitters at neuromuscular junctions in the gut. We have used a photoaffinity analogue of ATP, 3'-O-(4-benzoyl)benzoyl ATP or BzATP, that binds covalently to ATP receptors and inactivates them in the presence of light and a specific high-affinity VIP antiserum in order to examine the contributions of ATP and VIP to neurally induced relaxation in circular smooth muscle of the gastric fundus of the guinea pig. VIP and ATP caused dose-dependent relaxation; the effect of ATP was equal to that of its stable isostere, alpha, beta-methylene ATP, and was resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic P2-receptors. Relaxation induced by VIP was selectively inhibited by VIP antiserum (final dilution 1:120), while that induced by ATP was selectively inhibited by photoactivated BzATP. Relaxation induced by electrical field (i.e., neural) stimulation was inhibited by VIP antiserum only; photoactivated BzATP had no effect. Inhibition of neurally induced relaxation ranged from 86% (P less than 0.01) at the lowest frequencies to 34% (P less than 0.01) at the highest frequencies. Maximal field stimulation caused an 11-fold increase in VIP release from intramural neurons. The results strongly favor VIP as the neural mediator of gastric relaxation.
Mediation of muscarinic stimulation of pepsinogen secretion in the frog
Authors: Inoue M. , Fong J. , Shah G. , Hirschowitz B. I.
Published: December 2017

The in vitro release of pepsinogen secretion by the isolated esophagus of the American bullfrog was studied with an improved model system. The tissue was mounted in a double chamber that preserves mucosal polarity and provides both control and test segments, each 1 cm2 from the same tissue. Pepsinogen secretion was severalfold higher than previously found with mucosal strips and could be sustained for several hours. Bethanechol (BCh) caused concentration-dependent (0.1-50 microM) pepsinogen secretion with a Vmax of 74 +/- 12 micrograms X mg prot-1 X h-1 or 50-60% of total pepsinogen; Km was 3 microM and 500 microM BCh stimulated at less than the Vmax value. Atropine specifically blocked BCh and pA2 = 9.3. In the presence of 100 microM isobutylmethyxanthine, BCh produced a dose-dependent increase in tissue cAMP but not cGMP. BCh remained effective in Ca2+-free medium. In calcium-free medium EGTA concentration dependently (0.2-5 mM) suppressed the pepsinogen response to BCh. The evidence thus far suggests that cholinergic stimulation of pepsinogen secretion in the tissue acts via both cAMP and Ca2+. More specific studies would be required for absolute confirmation of either or both apparent mechanisms and to resolve how they interact.
Nicotine stimulation of protein secretion from isolated rat pancreatic acini
Authors: Majumdar A. P. , Davis G. A. , Dubick M. A. , Geokas M. C.
Published: December 2017

The secretion of amylase and trypsinogen from isolated rat pancreatic acini was greatly stimulated by 3–25 mM nicotine. In the presence of 12.5 mM nicotine, a concentration used in the study, amylase and trypsinogen release was increased by 95 and 400%, respectively, when compared with the corresponding control and showed further a preferential release of trypsinogen. A 90-min time course release of the enzymes revealed that in the presence of nicotine trypsinogen-to-amylase ratio remained two- to threefold elevated over that of the control throughout the incubation period. The nicotine-induced stimulation of trypsinogen and amylase release from the acini could not be blocked by 2.5 mM cycloheximide, a dose that inhibited overall acinar protein synthesis by about 85%. When isolated acini were incubated with [3H]leucine in the presence of nicotine, the released proteins revealed a fourfold higher radioactivity (dpm/microgram acinar DNA) than the control. Cycloheximide dramatically decreased this increment. The rate of release of 3H-pulse-labeled proteins from the acini was greatly accelerated by nicotine. It is concluded that nicotine stimulates the secretion of preformed zymogen granules and newly synthesized proteins from dispersed rat pancreatic acini in vitro.
Effects of E, F, and I series prostaglandins and analogues on growth of gastroduodenal mucosa and pancreas
Authors: Dembinski A. , Konturek S. J.
Published: December 2017

We investigated the effects of prostaglandins (PG) of E, F, and I series and their stable analogues on gastric acid secretion, serum gastrin level, and growth of gastroduodenal mucosa and pancreas in rats. Short-term administration (every 8 h for 48 h) of E and F series PGs and their stable analogues caused significant stimulation of DNA synthesis; prolonged PG treatment (every 8 h for 10 days) significantly increased weight and total DNA and RNA contents of the organs tested. PGs of E series were given in doses that inhibited gastric acid secretion about 50% and raised serum gastrin significantly; PGs of F series were injected in the same dose (1,000 micrograms/kg) as PGs of E series but did not affect acid secretion or serum gastrin. Short- or long-term treatment with PGI2 or its stable analogue (Hoe 892), injected in doses causing about 50% inhibition of acid secretion and significant increments in serum gastrin levels, failed to affect any of the growth-related parameters in the stomach, duodenum, or pancreas. We conclude that PGs of E and F (but not of I) series exhibit a marked stimulatory influence on growth of gastroduodenal mucosa and pancreas. These trophic effects appear to be unrelated to gastric secretion or serum gastrin release.
Acid secretion by frog gastric mucosa is electroneutral
Authors: Hersey S. J. , Sachs G. , Kasbekar D. K.
Published: December 2017

The action of a newly developed, specific inhibitor of the gastric proton pump, omeprazole, was investigated using intact frog gastric mucosa. Omeprazole was found to inhibit acid secretion, and the inhibition could be reversed with glutathione or 2-mercaptoethanol. Inhibition was not stimulus specific, occurring with histamine, carbachol, and forskolin. With hypertonic solutions bathing the mucosal surface, omeprazole inhibition of acid secretion did not change the tissue conductance, whereas inhibition by thiocyanate or cimetidine resulted in a significant decrease in conductance. With high-K+ (greater than 80 mM) sulfate solutions bathing both surfaces, omeprazole inhibition of acid secretion resulted in no change in transtissue potential difference. In chloride solutions, omeprazole caused an increase in potential difference and short-circuit current. These results provide evidence that the proton pump in frog gastric mucosa is electroneutral.
Effect of hypoxia on feline intestinal capillary permeability
Authors: Perry M. A. , Shepherd A. P. , Kvietys P. R. , Granger D. N.
Published: December 2017

The multiple-indicator dilution technique was used to investigate the permeability characteristics of capillaries in the cat small intestine during hypoxia. Reducing the arterial oxygen tension from 108 to 35 mmHg for 10 min increased the calculated equivalent pore radius of intestinal capillaries from 59 to 67 A. This effect was sustained for at least 15 min after the hypoxic episode. Hypoxia did not alter intestinal lymphatic protein clearance. Thus, the dimensions of the large pores did not change. This study demonstrates that 10 min of severe hypoxia increases vascular permeability in the small intestine and that this change occurs only in the small pores and is sustained, at least briefly, after restoration of normoxia. Hypoxia does not significantly change the permeability to macromolecules.
Jejunal-ileal differences in dopaminergic but not alpha-adrenergic antisecretory effects
Authors: Wahawisan R. , Gaginella T. S. , Wallace L. J.
Published: December 2017

Clonidine, an alpha-adrenergic agonist, and apomorphine, a dopaminergic agonist, inhibit water secretion in rat intestine induced by dibutyryl cAMP (DBcAMP) in situ. Apomorphine reversed DBcAMP-induced secretion in ileum and jejunum with ED50 values of 90 and 200 nM, respectively. ED50 values for clonidine's antisecretory effect were 32 and 2 microM in ileum and jejunum, respectively. The antisecretory effects of both clonidine and apomorphine were blocked by the alpha-adrenergic antagonist phentolamine and by the dopaminergic antagonists halo-peridol and sulpiride. Phentolamine was about 10-fold more potent against clonidine than against apomorphine in the ileum and the jejunum. Haloperidol and sulpiride were at least 10-fold more potent against apomorphine than against clonidine in the ileum. In contrast, in the jejunum, haloperidol was equally potent in blocking effects of both agonists, while sulpiride did not block the apomorphine effect. The data are consistent with the presence of both alpha 2-adrenergic and DA2-dopaminergic receptors that stimulate absorption in the ileum. In the jejunum, antisecretory effect appears to be mediated by an action on either an alpha 2-adrenergic or a dopaminergic receptor with characteristics different from those of peripheral DA1- or DA2-receptors.
Electrical properties of smooth muscle cell membrane of opossum esophagus
Authors: Kannan M. S. , Jager L. P. , Daniel E. E.
Published: December 2017

The electrical properties of the circular smooth muscle layer from the North American opossum esophagus (body) were studied in vitro by microelectrode recording techniques, both at rest and during stimulation of intramural inhibitory nerves. All observations were made at 37 degrees C in an Abe-Tomita partitioned bath on muscle strips dissected 2 cm orad of the lower esophageal sphincter. At rest, the potential of the smooth muscle cell membrane was -49 +/- 4 mV (mean +/- SE); the length constant and the time constant were 2.0 +/- 0.6 mm and 120 +/- 16 ms, respectively. The inhibitory junction potential (IJP) elicited by stimulation of intramural nerves was followed by a "rebound" or "off" response, characterized by a membrane depolarization on which spikes were superimposed and concomitant mechanical activity of the preparation that usually caused dislocation of the recording microelectrode. The maximal IJP amplitude was 35 mV, and the response reversed at a membrane polarization to -90 mV, suggesting that the IJP was due to an increase of the permeability toward potassium ions. The invariability of the IJP latency at different distances from the stimulating electrodes (1.25-4 mm) suggests that the latency is largely due to diffusion of transmitter from nerve varicosities to postsynaptic receptor sites. Depending on the rate, prolonged stimulation caused fusion of IJP or a continuous hyperpolarization of the membrane. The hyperpolarization faded with time, but off responses were only observed after terminating stimulation. The passive electrical properties of the membrane are comparable with those of other gastrointestinal smooth muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Laser-Doppler blood flowmetry of intestinal mucosal hyperemia induced by glucose and bile
Authors: Shepherd A. P. , Riedel G. L.
Published: December 2017

To determine whether the functional hyperemia evoked by solute transport is confined to the intestinal mucosa or whether blood flow increases throughout the bowel wall, we measured blood flow in the mucosa and muscularis-serosa with laser-Doppler velocimetry. Ileal loops were vascularly isolated in pentobarbital sodium-anesthetized dogs. Total blood flow to the loop was measured electromagnetically, while blood flow in the superficial mucosa and muscularis-serosa was monitored by laser-Doppler velocimetry. Perfusion pressures and arteriovenous oxygen difference were also recorded continuously. When a mixture of 5% bile and glucose was placed in the lumen of the isolated loop, total blood flow and oxygen uptake increased 21 and 62%, respectively. During this hypermetabolic state, laser-Doppler measurements indicated blood flow in the muscularis-serosa fell by 10%, but blood flow in the mucosa increased 42%. These findings with laser-Doppler velocimetry confirm earlier studies in which the radioactive microsphere technique indicated that low-fat, low-protein test meals induce a postprandial hyperemia confined to the mucosal circulation. These findings also demonstrate a metabolic flow-controlling mechanism closely linked to the absorptive process.
Induction in vitro of a specific pattern of jejunal propulsive behavior by cholecystokinin
Authors: Weems W. A. , Seidel E. R. , Johnson L. R.
Published: December 2017

Experiments were conducted in vitro to determine whether arterial infusion of the C-terminal octapeptide of cholecystokinin (CCK-8) into cat jejunal segments could elicit propulsive behavior when a segment must do hydrostatic work to expel fluid. Oral and aboral ends of jejunal segments, 17 cm in length, were connected to a propulsion evaluation system that imposed input-output conditions of constant capacitance and negligible resistance. Infusion of 1 X 10(-10) to 3 X 10(-9) M CCK-8 produced an initial simultaneous ejection of approximately equal volumes of fluid from both ends of the segments. This reduction in luminal volume lasted for approximately 4 min. Concurrent with this initial reduction in luminal volume were phasic ejections of fluid that often did not occur simultaneously or with equal magnitude from both ends of a segment. This pattern persisted throughout the period of CCK-8 infusion. Arterial infusion of atropine sulfate (10(-6) M) or hexamethonium sulfate (2.8 X 10(-7) M) prevented the induction of propulsive behavior by CCK-8. These results indicate that arterial infusion of CCK-8 can induce a specific pattern of jejunal propulsive behavior by triggering neural activity in the enteric nervous system and that CCK-8 may have a physiological role in regulating propulsion.
Carbobenzoxy amino acids: structural requirements for cholecystokinin receptor antagonist activity
Authors: Maton P. N. , Sutliff V. E. , Jensen R. T. , Gardner J. D.
Published: December 2017

We used dispersed acini prepared from guinea pig pancreas to examine 28 carbobenzoxy (CBZ) amino acids for their abilities to function as cholecystokinin receptor antagonists. All amino acid derivatives tested, except for CBZ-alanine, CBZ-glycine, and N alpha-CBZ-lysine, were able to inhibit the stimulation of amylase secretion caused by the C-terminal octapeptide of cholecystokinin. In general, there was a good correlation between the ability of a carbobenzoxy amino acid to inhibit stimulated amylase secretion and the ability of the amino acid derivative to inhibit binding of 125I-cholecystokinin. The inhibition of cholecystokinin-stimulated amylase secretion was competitive, fully reversible, and specific for those secretagogues that interact with the cholecystokinin receptor. The potencies with which the various carbobenzoxy amino acids inhibited the action of cholecystokinin varied 100-fold and CBZ-cystine was the most potent cholecystokinin receptor antagonist. This variation in potency was primarily but not exclusively a function of the hydrophobicity of the amino acid side chain.