bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of electrolyte transport in rat ileum
Authors: Tai Y. H. , Decker R. A.
Published: December 2017

The short-circuit current (Isc), potential difference (PD), tissue conductance (Gt), and Na and Cl fluxes in the short-circuit state across rat ileum were studied in Ussing chambers using a variety of bathing solutions. In Ringer solution, Isc exceeded net Na absorption and net Cl secretion occurred. Addition of 10 mM glucose increased Isc, PD, Gt, and net Na absorption, which accounts for 70% of the increase in Isc. Removal of HCO3 from Ringer solution did not alter any parameters but increased net Cl secretion due to a decrease in mucosal-to-serosal Cl flux. Reduction by 50% of the [Cl] in HCO3-free solution decreased the net Cl secretion to the level in Ringer solution and increased net Na absorption. Removal of Cl decreased Isc to the value of the net Na absorption and decreased the Na influx across the mucosal membrane by 39%. Isc and PD were near zero and net Cl absorption was observed in a Na-free solution. These results are consistent with the transport mechanism that consists of 1) an electrogenic Na absorptive process that accounts for the Isc, 2) a neutral NaCl-coupled secretory process, and 3) a system by which HCO3- secretion exchanges for Cl- absorption.
Effects of nutrients, endogenous secretions, and fasting on in vitro glucose uptake
Authors: Kotler D. P. , Levine G. M. , Shiau Y. F.
Published: December 2017

The effect of luminal nutrients, endogenous secretions, and metabolic balance on the initial velocity of glucose uptake was measured in everted rings of rat intestine. Animals were fed either by total parenteral nutrition (TPN), or into the midjejunum for 7 days, or fasted for 72 h. Luminal feeding resulted in higher midjejunal glucose uptake per milligram of protein, DNA, and centimeter gut length, when compared to fasting or TPN. Kinetic analysis revealed a higher "apparent" Vmax in the luminally fed group, whereas the "apparent" Km was similar in all groups. Diversion of the pancreaticobility secretions did not affect glucose uptake in luminally fed or TPN-fed animals. TPN-fed and fasted animals had similar glucose uptake. Luminal feeding did not have a remote effect on glucose uptake in intestine isolated from the nutrient stream. The results indicate that luminal nutrients maintain carrier-mediated glucose transport after direct contact with the mucosa. Overall metabolic balance and pancreaticobiliary secretions do not affect carrier-mediated glucose transport. The nutrient effect appears to involve an increased number of glucose carriers per cell without a change in carrier affinity for glucose.
Histamine responsiveness of isolated gastric glands
Authors: Chew C. S. , Hersey S. J. , Sachs G. , Berglindh T.
Published: December 2017

Gastric glands isolated from rabbit were employed to perform a pharmacological characterization of the histamine receptor associated with physiological and biochemical responses in gastric cells. Five separate response parameters were characterized using histamine analogues and histamine antagonists. The following parameters were studied: respiration, accumulation of the weak base aminopyrine, adenylate cyclase activity, cAMP accumulation, and the uptake of histamine. All parameters were examined for agonist and antagonist potency using dose-response curves, ED50 and pA2 values. Comparison of the ED50-agonist and pA2-cimetidine values showed a remarkable similarity for respiration, aminopyrine accumulation, adenylate cyclase activity, and cAMP accumulation. The agonist potency sequence and pA2 values for H2- vs. H1-receptor antagonists characterized the histamine receptor associated with these four parameters as being of the H2 type. Moreover, the similarity of pharmacological characteristics provides evidence for a similar, if not common, receptor for these responses. The histamine uptake system shows a generally lower affinity for most agonists. Although the general agonist potency sequence is similar to the other parameters, notable exceptions were found for antagonists and the typical H2-agonist, dimaprit. Thus, the uptake system does not appear to be related directly to the activation of secretion and the carrier binding site cannot be simply defined by H1 or H2 properties.
Triton-induced hyperlipidemia: a model for studies of intestinal lipoprotein production
Authors: Holt P. R. , Dominguez A. A.
Published: December 2017

To estimate intestinal very low-density lipoprotein (VLDL) contribution to the circulating plasma triglyceride (TG) pool, mesenteric, hepatic, and total TG production rates were measured in mesenteric lymph-cannulated male rats after Triton WR-1339 blockage of systemic VLDL metabolism. The intestinal contribution (4.92 +/- 0.5 mg TG/h) was calculated to be 19% of total TG production rate. Triton WR-1339 administration caused profound hyperlipoproteinemia but did not alter total lymph TG or VLDL apoprotein output. The percent of lymph VLDL apoprotein present as apo A-I and apo A-IV fell dramatically after Triton with a concomitant increase in apo E and apo C peptides. Studies in this Triton-treated rat model suggest that the intestinal contribution to systemic TG formation is small but that changes in circulating apolipoproteins may alter the composition of intestinal VLDL.
Effect of glucagon on ion transport in mouse intestine
Authors: Kaufman M. E. , Dinno M. A. , Huang K. C.
Published: December 2017

Effects of glucagon (GN) on short-circuited mouse intestine were studied. GN (30 microgram . ml-1), added to the serosa of intestine mounted in an Ussing chamber and bathed in glucose-free Ringer, induced significant increases of 43% in serosal-to-mucosal Cl- flux (Js leads to m Cl), 315% in net Cl- secretion (Jnet Cl), 85% in net residual flux (J net R), 61% in short-circuit current (Isc), and 44% in open-circuit potential difference (PD). The mucosal-to-serosal Cl- flux and both unidirectional Na+ fluxes (Jm leads to s Na and Js leads to m Na) were unchanged. In a glucose Ringer bathing medium, GN exhibited no significant effects on ion fluxes and electrical parameters. To eliminate the possibility that observed GN-induced changes in PD and Isc were partially due to changes in membrane surface charge, the effects of GN in Cl- -free Ringer were studied. Under these conditions, GN had no effect on electrical parameters. Furthermore, GN elicited no effect on cAMP levels in either the presence or absence of glucose. These findings suggest that 1) the effect of GN on Jnet Cl is masked in the presence of glucose, 2) GN-induced increases in Isc and PD are a reflection of the increase in Jnet Cl and are neither due to changes in membrane surface charge nor to an increase in net Na+ flux, and 3) GN-induced secretory diarrhea is in part due to changes in electrolyte transport.
Effects of portacaval shunt and transposition on fatty acid and cholesterol biosynthesis in rat liver
Authors: Pector J. C. , Winand J. , Dehaye J. P. , Christophe J.
Published: December 2017

Male rats underwent either portacaval shunt or portacaval transposition; in both cases, sham-operated pair-fed rats served as controls. Three weeks after a portacaval shunt, fasting serum values of glucose (-35%) and cholesterol (-24%) were lower, and fasting plasma glucagon was higher (+65%). The wet weight of the liver and its total content in DNA, RNA, and protein decreased by 43, 40, 43, and 48%, respectively. The supernatant of liver obtained after centrifugation at 700 g incorporated less [1-14C]acetate (-56%) into fatty acids and less [1-14C]acetate (-94%) and [2-14C]mevalonate (-37%) into cholesterol. The activity of acetyl CoA carboxylase was reduced by 56%. The in vivo incorporation of [3H]H2O into liver fatty acids was 83% lower and that into liver cholesterol was 39% lower than in pair-fed controls. Several of the preceding parameters, including in vitro and in vivo labeling of hepatic fatty acids and cholesterol, were found to be mostly normal in rats with portacaval transposition. These data suggest that the reduction of fatty acid and cholesterol biosynthesis in the liver of rats with portacaval shunt was due to the reduction of total hepatic blood flow rather than to the diversion of portal blood constituents.
Portal venous transport of long-chain fatty acids absorbed from rat intestine
Authors: McDonald G. B. , Saunders D. R. , Weidman M. , Fisher L.
Published: December 2017

We studied the route of transport of long-chain fatty acids (LCFA) from the rat intestine. Lauric (12:0), myristic (14:0), palmitic (16:0), stearic (18:0), linoleic (18:2), and linolenic (18:3) acids were infused intraduodenally for 4 h as micellar solutions into unanesthetized thoracic duct-fistula rats. Proportionally more of each LCFA was transported by the portal vein at infusion rates of 0.3 mumol/h than at 15 mumol/h. Of the LCFA absorbed at low rates of infusion, 72% of lauric, 58% of myristic, 41% of palmitic, 28% of stearic, 58% of linoleic, and 68% of linolenic acid bypassed the lymphatic pathway. To test the inference that 58% of absorbed linoleate was transported by the portal vein, [14C]linoleic acid was infused at 0.3 or 15 mumol/h into unanesthetized rats equipped with both thoracic duct and portal venous fistulas. Portal venous blood (0.1 ml) was withdrawn every 30 min for 4 h. Proportionally more [14C]linoleate was recovered in portal blood at the low infusion rate. To examine the morphology of fat absorption, segments of rat jejunum in anesthetized rats were infused with micellar linoleic acid at 3 or 150 mumol/h. At 3-mumol/h infusion rate, an appearance identical to the fasting state was seen by electron microscopy. At 150 mumol/h, many larger chylomicron-sized particles appeared in absorptive cells, intercellular spaces, and lymphatics. We conclude that a substantial proportion of unsaturated LCFA is transported from rat intestine in portal venous blood.
Ba2+ inhibition of electrogenic Cl- secretion in vitro frog and piglet gastric mucosa
Authors: McLennan W. L. , Machen T. E. , Zeuthen T.
Published: December 2017

Gastric mucosae from frogs and newborn pigs were used for in vitro investigation of the effects of Ba2+ (10 microM to 7 mM) on transepithelial potential difference (PD), resistance and conductance (G), short-circuit current (Isc), H+ secretion, and transepithelial fluxes of 36Cl-. Ba2+ in the serosal, but not the mucosal, solution of both preparations caused PD, G, Isc, and Cl- secretion (JnetCl, Isc conditions) to decrease, while H+ secretion remained constant. Because the oxyntic cells were most likely the site of action for Ba2+, these cells must have the capacity to secrete Cl- in excess of H+ ions. The inhibitory effect of Ba2+ was not due to competition in the serosal membrane by Ba2+ for surface charges, Ca2+ sites, Na+ sites, or Cl- sites. When [K+] in both the mucosal and serosal solutions or in just the serosal solution ([K+]s) alone was increased to 10 mM, the inhibitory effects of low [Ba2+] were reduced; however, at higher [Ba2+], Isc was stimulated. At least part of the Ba2+ effect seems to be due to blockage of K+ channels in the serosal membrane of oxyntic cells. High [K+]s also caused decreased PD and Isc (but increased G) with no change in H+ secretion. It is proposed that during Isc conditions, JnetCl involves a neutral Na+-dependent accumulation of Cl- within oxyntic cells and a passive, conductive efflux fromthe cells into the mucosal solution. Ba2+ and high [K+] may alter this transport by depolarizing and, under certain conditions, hyperpolarizing intracellular voltage.
Canine jejunal absorption and transit during interdigestive and digestive motor states
Authors: Sarr M. G. , Kelly K. A. , Phillips S. F.
Published: December 2017

To determine whether absorption varies during interdigestive and digestive motor states, an isolated, 75-cm segment of jejunum was perfused in each of five dogs with an isosmolar solution of 130 mM glucose, 80 mM NaCl, and [3H]polyethylene glycol (PEG). Effluent was collected from the distal stoma during 10-min intervals. Electrical activity of the segment was recorded concurrently. Transit times were assessed with boluses of [14C]-PEG. The dogs were studied during phase I, phase II, and phase III of the interdigestive myoelectric complex and also after a 200-g meal of liver. Absorption during fasting was greatest during phase I and least during phase III of the interdigestive myoelectric complex; feeding enhanced absorption over that seen during any phase of fasting. Transit was slowest in phase I of fasting and most rapid during phase III; transits during phase II of fasting and after feeding were roughly equal. Using indicator-dilution calculations, static volumes were greatest and mean flows slowest during phase I. Thus, jejunal absorption during fasting decreased as transit increased sequentially with the interdigestive myoelectric phases. However, after feeding, although transit time was similar to phase II, absorption was greater.
Motilin-independent ectopic fronts of the interdigestive myoelectric complex in dogs
Authors: Poitras P. , Steinbach J. H. , VanDeventer G. , Code C. F. , Walsh J. H.
Published: December 2017

We have studied in four conscious dogs the relationship between circulating concentrations of motilin and the activity front (phase III) of the interdigestive myoelectric complex. During fasting, cyclic peaks of motilin secretion were concomitant in every instance with the initiation of activity fronts that began in the stomach or duodenum. When somatostatin was administered at doses of 5, 2.5, or 0.625 microgram x kg-1 x h-1 for 3 h, motilin concentrations were stabilized at lowered levels and no activity fronts occurred in the duodenum. Somatostatin also inhibited the stimulatory effects of exogenous motilin on the entire small intestine. During somatostatin infusion, however, ectopic fronts began in the jejunum and were propagated to the cecum despite low motilin concentration. After a 100-g meat meal, the cyclic increase of motilin was interrupted and no activity fronts were observed in the duodenum, but ectopic fronts started lower in the small intestine. Our study supports the hypothesis that motilin induces activity fronts in the canine duodenum, but it shows that ectopic fronts are not controlled by motilin.
Secretory response of the rabbit pancreas to cholecystokinin stimulation
Authors: Iacino D. , Scheele G. A. , Liebow C.
Published: December 2017

To test the capability of the pancreas to change the proportions of proteins secreted in response to acute stimulation, we examined the effect of cholecystokinin-pancreozymin stimulation on the relative discharge of 16 radiolabeled secretory proteins from the in vitro rabbit pancreatic gland. [35S]-methionine was added to the bathing medium 4 h prior to the experimental period. Secretion was then collected from the pancreatic duct for two 1-h basal periods and for two 20-min periods following stimulation with 5.1 mM cholecystokinin. Proteins were separated by two-dimensional isoelectric focusing/sodium dodecyl sulfate gradient gel electrophoresis, and the proportion of each radiolabeled protein in the secretion was determined in each period. Statistical analysis of the relative distribution of radioactive proteins in secretion showed an increased variability in the distribution of secreted proteins following stimulation (P < 0.005). Procarboxypeptidase A, a protein tentatively identified as an acidic form of chymotrypsinogen, and a basic form of chymotrypsinogen were significantly more stimulated than the average radiolabeled protein by 25, 31, and 17%, respectively, whereas the acidic form of trypsinogen was significantly less stimulated by 18%.
Cholecystokinin-induced desensitization of enzyme secretion in dispersed acini from guinea pig pancreas
Authors: Abdelmoumene S. , Gardner J. D.
Published: December 2017

Incubating dispersed acini from guinea pig pancreas with cholecystokinin and then washing the cells to remove cholecystokinin reduced the subsequent stimulation of amylase secretion caused by pancreatic secretagogues, whose actions are mediated by release of cellular calcium (i.e., cholecystokinin, carbamylcholine, bombesin, litorin, physalaemin, and A23187), but did not alter the stimulation caused by secretagogues whose actions are mediated by cAMP (i.e., vasoactive intestinal peptide and secretin). This cholecystokinin-induced desensitization was reversible, and the onset of the process as well as its reversal were time- and temperature-dependent changes. The concentrations of cholecystokinin required to cause desensitization were greater than those required to cause maximal stimulation of amylase secretion, and this finding suggests that the submaximal stimulation of enzyme secretion seen with supramaximal concentrations of cholecystokinin may be caused by cholecystokinin-induced desensitization.
Ontogenesis of intestinal bile salt absorption in the neonatal rat
Authors: Little J. M. , Lester R.
Published: December 2017

In vitro uptake of taurocholate by weanling rat ileum was characterized. The neonatal development of the ileal mechanism was determined, and the effect of steroid treatment on this development was assessed. Mucosal uptake of taurocholate by ileum of 26-day-old and adult rats was linear with time and, when measured as a function of concentration, tended toward a plateau. Mucosal concentration of taurocholate was significantly reduced by metabolic inhibitors and was competitively inhibited by taurochenodeoxycholate. The capacity to concentrate taurocholate in ileal mucosa was undemonstrable in 12-day-old neonates, first appeared at 15 days, and reached adult levels by 26 days of age. Mucosal uptake of taurocholate by ileum of 12-day-old offspring of steroid-treated mothers or of 12-day-old neonates given dexamethasone directly was significantly increased over control values. The results indicate that the ileal bile salt absorption found in weanling rats is an active process that does not begin to develop in neonatal rats until 15 days after birth, and that the appearance of ileal active transport can be accelerated by maternal or neonatal steroid treatment.
Effect of age on uptake of homologous series of saturated fatty acids into rabbit jejunum
Authors: Thomson A. B.
Published: December 2017

The effect of age on the rate of uptake (Jd) of a homologous series of saturated fatty acids into rabbit jejunum was determined in suckling, mature, and old animals. A previously validated in vitro technique was used, and the bulk phase was stirred at different rates to vary the effective resistance of the unstirred water layer (UWL). When UWL was high, Jd of fatty acids was greater in old than in young animals; Jd was greatly increased when UWL was low, and Jd was not higher in the suckling and mature rather than the old animals. At each rate of stirring UWL was lowest in the suckling rabbits and highest in the old animals. The values of Jd were corrected for UWL, yielding estimates of the true passive permeability properties of the membrane. From these values, the incremental free energy change associated with the addition of each -CH2- group to the fatty acid chain was 50% higher in the suckling and mature animals than in the old animals, and the estimated surface area of the jejunal membrane was also higher in the suckling and mature animals. Variations in UWL had a profound effect on the Jd of passively absorbed fatty acids, and failure to account for UWL leads to gross underestimation of the permeability properties of the jejunal microvillus membrane. Furthermore, the difference between the true and apparent passive permeability coefficients becomes greater as the fatty acid chain length increases. The results suggest that discrepancies in uptake of fatty acids in animals of different ages are explained by differences in the passive permeability properties and functional surface area of the membrane and by differences in the overlying UWL.
Hypothalamic hyperphagia and obesity in rats with jejunoileal bypass
Authors: Sclafani A. , Koopmans H. S. , Appelbaum K. A.
Published: December 2017

Jejunoileal bypass or sham surgery was performed in adult female rats followed 35 days later by ventromedial hypothalamic (VMH) knife cut or sham surgery (forming groups Bypass-VMH, Bypass-Sham, Sham-VMH, and Sham-Sham). Bypassed rats receiving VMH cuts (Bypass-VMH group) ate more food and gained more weight than did either Bypass-Sham or Sham-Sham groups. The hyperphagia and obesity of the Bypass-VMH rats was, however, substantially less than that of the sham bypass VMH cut rats (Sham-VMH group). Bypass-VMH rats that had their intestinal tract reconnected increased their food intake and ultimately became as obese as the Sham-VMH rats. Two additional groups received VMH knife cut or sham surgery followed 50 days later by jejunoileal bypass surgery (VMH-Bypass and Sham-Bypass groups). At the time of the bypass the VMH-Bypass group was hyperphagic and obese, but after surgery they underate and lost weight until they eventually stabilized their body weight at a level below that of the Sham-Bypass group. The body weight of the VMH-Bypass group was also 167 g less than that of the Bypass-VMH group. Thus, the order of surgery significantly influences the food intake and body weight level of rats with VMH knife cuts and jejunoileal bypass.
Uptake and incorporation of phosphate by frog gastric mucosa
Authors: Durbin R. P. , Hanzel D.
Published: December 2017

Labeled inorganic phosphate (32Pi) was used to follow uptake and incorporation of phosphate into high-energy intermediates of isolated bullfrog gastric mucosa. Dependence of uptake on levels of external Pi showed both saturable nonsaturable components. Measurements at 25 microM Pi, a level at which the saturable component was predominant, showed a strong dependence of Pi uptake on external Na+ and pH. Labeling of adenosine 5'-triphosphate (ATP) and creatine phosphate was rapid, followed by labeling of adenosine 5'-diphosphate, probably by way of adenylate kinase. Both alkaline nutrient pH and the uncoupling agent, dinitrophenol, reduced labeling of ATP with a concomitant inhibition of acid secretion. A feasible interpretation is that dinitrophenol acts by diminishing mitochondrial production of ATP, whereas alkaline pH reduces the utilization of ATP by the K+-ATPase considered to be responsible for acid production. The results thus agree with the hypothesis that ATP is the immediate substrate for secretion: only a part of the tissue ATP is directly available to the acid-producing mechanism, however.
Physiological significance of glutathione S-transferases
Authors: Kaplowitz N.
Published: December 2017

The glutathione S-transferases represent a group of closely related soluble enzymes that seem geared to detoxification. These enzymes, which are most abundant in the liver but are found in most cells, catalyze the interaction between glutathione and a broad spectrum of electrophilic reactive drugs, carcinogens, and metabolites. In addition, a more speculative aspect of the detoxification role of these proteins is the covalent interaction between certain reactive carcinogen metabolites and the enzymes. Finally, as an aspect of their broad specificity, the transferases bind a broad spectrum of nonsubstrate ligands including bilirubin. On this basis a role in hepatic organic anion transport has been proposed for the transferases (previously known as Y protein or ligandin). It is now recognized that the transferases may affect net uptake by the liver by minimizing back diffusion. Much work remains to more precisely define the regulation and role(s) of this enzyme system in vivo.
Clearance of circulating anionic and cationic pancreatic trypsinogens in the rat
Authors: Brodrick J. W. , Largman C. , Geokas M. C. , O'Rourke M. , Ray S. B.
Published: December 2017

The kinetics and mechanism of clearance of pancreatic cationic and anionic trypsinogens from the circulation have been investigated in a rat model. 125I-labeled rat cationic trypsinogen is cleared from the bloodstream with a half-life of approximately 4 min. In contrast, 125I-labeled rat anionic trypsinogen has a half-life in the circulation of approximately 55–60 min. The major site of clearance for both enzymes is the kidney. Neither zymogen binds to plasma proteins to a significant extent over a period of three half-lives. The relative rates of clearance of these zymogens from the circulation appears to correlate with their respective isoelectric points.
Role of nutrient HCO3(-) in protection of amphibian gastric mucosa
Authors: Schiessel R. , Merhav A. , Matthews J. B. , Fleischer L. A. , Barzilai A. , Silen W.
Published: December 2017

In in vitro bullfrog fundic mucosa inhibited with 10(-3) M metiamide and exposed to a luminal pH of 2 a progressive slow decline in potential difference (PD) and short-circuit current (Isc) and a rise in resistance (R) were observed when the nutrient solution (N) contained 18 mM HCO3(-), but these changes were restored by an N containing 50 mM HCO3(-). Substitution of PO4(3-) or N-tris(hydroxymethyl)-methyl-2-aminoethanesulfonic acid for NHO3(-) in N caused a rapid drop in PD and Isc in inhibited tissues, changes that could be prevented by 10(-4) M histamine. Ulceration occurred more frequently in metiamide-inhibited gastric sacs exposed to artificial gastric juice with an N of 18 mMHCO3(-) than with 50 mM HCO3(-), but histamine prevented ulceration in the 18 mM HCO3(-) solution. JnetCl approximated Isc under most experimental conditions in inhibited mucosa and was reduced dramatically as were both Jn leads to sCl and Js leads to nCl when HCO3(-) was removed from N. In histamine-stimulated tissues, removal of nutrient HCO3(-) did not influence Cl- transport. Our results are consistent with the proposal that HCO3(-) in N supports normal Cl- flux and that the alkaline tide of actively secreting oxyntic cells can do the same in the absence of ambient HCO3(-).
Adrenergic stimulation and blockade in colonic circulation of the rhesus monkey
Authors: Kerr J. C. , Swan K. G.
Published: December 2017

Adrenergic stimulation and blockade on inferior mesenteric arterial blood flow (Q) were measured in anesthetized rhesus monkeys. Control Q was 25 +/- 2 (mean +/- SE) ml/min; aortic and portal venous pressures were 121 +/- 5 and 6.5 +/- 1.0 mmHg. Calculated inferior mesenteric arterial resistance was 5.10 +/- 0.42 peripheral resistance units. Norepinephrine (N), 10(-3) to 1.0 microgram/kg intra-arterially, caused dose-dependent decreases in Q. Epinephrine (E) increased Q at 10(-3) microgram/kg in 60% of the animals studied and decreased Q at the higher doses (10(-2) to 1.0 microgram/kg). Isoproterenol (I) increased Q at all four doses studied. Ten-minute infusions of N and E (0.5 microgram x kg-1 x min-1) caused sustained decreases, and I caused sustained increases in Q. Autoregulatory escape was not observed. alpha-Adrenergic receptor blockade (phenoxybenzamine) attenuated the vasoconstrictor responses to N, but did not "reverse" the vasoconstrictor response to E (vasodilation). beta-adrenergic receptor blockade (propranolol) attenuated the vasodilator responses to I, but did not alter significantly the responses to E or N. These data indicate that in the monkey colonic circulation, alpha-adrenergic receptor stimulation causes vasoconstriction and beta-adrenergic receptor stimulation causes vasodilation.
Insulin action in pancreatic acini from streptozotocin-treated rats. I. Stimulation of protein synthesis
Authors: Korc M. , Iwamoto Y. , Sankaran H. , Williams J. A. , Goldfine I. D.
Published: December 2017

Pancreatic acini were prepared from rats rendered diabetic with streptozotocin. In this tissue, insulin stimulated [3H]leucine incorporation into protein. The full effects of insulin on this function were not immediate but increased linearly with time for up to 2 h of incubation. Insulin had a detectable effect on l eucine incorporation at 50 pM, a half-maximal effect at 0.7 nM, and a maximal effect at 30 nM. Desdipeptide proinsulin was only 10% as potent as native insulin in stimulating [3H]leucine incorporation, whereas proinsulin and desoctapeptide insulin were only 1% as potent. Insulin also increased the incorporation of [3H]valine and [35S]methionine into protein but did not increase the influx of either [14C]cycloleucine or alpha-[3H]aminoisobutyric acid. These observations suggested that the increased incorporation of labeled amino acid into protein reflected stimulation of protein synthesis rather than stimulation of amino acid transport. Furthermore, insulin at 1.67 nM significantly increased the acinar cell concentration of amylase. The present findings are consistent therefore with the concept that insulin regulates pancreatic exocrine functions, including protein and enzyme synthesis.
Insulin action in pancreatic acini from streptozotocin-treated rats. II. Binding of 125I-insulin to receptors
Authors: Sankaran H. , Iwamoto Y. , Korc M. , Williams J. A. , Goldfine I. D.
Published: December 2017

The binding of 125I-insulin to its receptors was investigated with isolated pancreatic acini obtained from diabetic rats under incubation conditions identical to those used to study the effects of insulin on acinar cell protein synthesis. Binding was specific, time dependent, reversible, and linearly related to the acinar protein content. Degradation of insulin after 30 min of incubation was less than 10% of the total hormone present in the incubation medium. 125I-insulin dissociated from acini with a one-half time of 9 min. Unlabeled insulin at 83.5 nM accelerated the rate of dissociation of labeled insulin. 125I-insulin binding to acini was competitively inhibited by insulin and its analogues in proportion to their biological potencies. Scatchard analysis revealed a major class of insulin-binding sites with a Kd of 1.6 nM; maximal stimulation of protein synthesis was observed when > 90% of these high-affinity receptors were occupied. These studies indicate, therefore, that insulin binding to receptors on pancreatic acini can be correlated with subsequent regulation of biological functions.
Histamine regulation of adenylyl cyclase of enriched rat gastric parietal cells
Authors: Thompson W. J. , Chang L. K. , Rosenfeld G. C.
Published: December 2017

Rat gastric parietal cells were isolated to 90% or greater purity by discontinuous gradient ultracentrifugation in sucrose-Ficoll. Adenylyl cyclase activity was initiated by histamine in the presence of 5'-guanylyl imidodiphosphate, but not by pentagastrin or acetylcholine. The concentration of histamine needed for half-maximal activation of adenylyl cyclase was 38 microM. The histamine H2-receptor antagonist, metiamide, inhibited histamine (100 microM) activation with a Ki of 0.9 microM. The effects of other histamine agonists and antagonists suggest that presence of H2-type histaminic receptors on parietal cells. Adenylyl cyclase activity was also stimulated by isoproterenol, norepinephrine, and epinephrine, but not by methoxamine. Half-maximal activation by isoproterenol occurred at 0.5 microM. Propranolol, but not phentolamine, prevented activation by these agents, indicating the presence of beta-adrenergic receptors on parietal cells. Prostaglandins E2 stimulated adenylyl cyclase of partially purified (30%), but not the enriched (90%), parietal cell populations.
Intestinal and metabolic effect of 1,25-dihydroxyvitamin D3 in normal adult rat
Authors: Lee D. B. , Walling M. M. , Levine B. S. , Gafter U. , Silis V. , Hodsman A. , Coburn J. W.
Published: December 2017

We examined the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on intestinal 45Ca and [32P]phosphate uptake in normal and mineral- and vitamin D-replete adult rats. The results indicate that 45Ca uptake by adult rat duodenum was stimulated by "physiological" doses of 1,25(OH)2D3. With increasing dosage of 1,25(OH)2D3, 45Ca uptake also became stimulated first in the colon and then in the jejunum and ileum. The increase in duodenal and jejunal 45Ca uptake was paralleled by an increase in [32P]phosphate uptake, but this parallelism was not always seen in the ileum and was never observed in the colon. The dissociated calcium and phosphate transport response to 1,25(OH)2D3 stimulation in the colon was further confirmed by the measurement of transmural fluxes using a modified Ussing technique. These responses to 1,25(OH)2D3 are similar to those observed in younger vitamin D-deficient rats. However, supraphysiological doses of 1,25(OH)2D3 caused weight loss in normal adult rats, whereas the same metabolite, even when given in large doses, led to weight gain in vitamin D-deficient rats. We propose the normal adult rat as an additional model for evaluating the biological action of 1,25(OH)2D3.
Secretagogue-induced changes in subcellular Ca2+ distribution in isolated pancreatic acini
Authors: Dormer R. L. , Williams J. A.
Published: December 2017

In a prior study, we demonstrated that pancreatic secretagogues increased both the uptake into and washout of 45Ca2+ from isolated mouse pancreatic acini. The net result of these processes was an initial fall in total acinar cell Ca2+ content. In the present study, we have employed subcellular fractionation of acini under conditions that minimized posthomogenization redistribution of Ca2+ in order to localize those organelles involved in intracellular Ca2+ fluxes. Homogenization and differential centrifugation of acini, preloaded with 45Ca2+ and subjected to a period of washout, showed that carbachol induced an increased loss of 45Ca2+ from all fractions isolated. The high-speed microsomal fraction lost 45Ca2+ to a greater extent than did whole acini; measurement of total Ca2+ by atomic absorption spectrometry showed a net loss of Ca2+ from this fraction. Purification of the lower-speed fractions indicated that carbachol increased 45Ca2+ exchange with both zymogen granules and mitochondria, but net Ca2+ levels in these organelles were unchanged. It was concluded that stimulation of pancreatic acini by carbachol results in the release of calcium from a microsomal compartment leading to a rise in cytoplasmic Ca2+, increased exchange with granule and mitochondrial Ca2+, and increased efflux of Ca2+ from the cell.
Experimental analysis of hydrogen ion diffusion in gastrointestinal mucus glycoprotein
Authors: Pfeiffer C. J.
Published: December 2017

Experiments were undertaken to test the hypothesis that mucus glycoproteins retard the diffusion of hydrogen ions, a possible protective action of gastric mucus. Mucus and mucus glycoproteins (visible mucus, crude mucin, mucus glycoprotein fractions) were evaluated in two devices designed for this test, a linear diffusion chamber and a hydrogen ion flux chamber. The linear diffusion chamber assessed ion diffusion from a point source through mucus glycoproteins to a H+ detector. A mathematical model of diffusion, based on Fick's law, was adapted to characterize diffusion in this chamber. The H+ flux chamber assessed H+ flux rates across a steep concentration gradient through controlled amounts of mucus glycoprotein. With the exception of human sulfomucin, tested only at dilute concentrations and only in the flux chamber, both procedures indicated that mucosubstances retarded, in a dose-related manner, diffusion of hydrogen ions. Experiments on buffering by crude porcine gastric mucin did not demonstrate significant buffering under physiological conditions. Thus, the present experimental data, the principles of which should be extrapolative to the mucous barrier at the biological level, suggest that mucus glycoproteins can in fact inhibit the diffusion of hydrogen ions.
Four basic characteristics of the gastrin-cholecystokinin system
Authors: Rehfeld J. F.
Published: December 2017

The gastrointestinal peptide hormones, gastrin and cholecystokinin (CCK), display four molecular characteristics. 1) Homology. Sequences of the primary structures are identical. Because the identity comprises the active site, the homology is functionally important. The homology reflects evolution from a common ancestor. 2) Heterogeneity. Each hormone exists in different molecular forms in any single species. The heterogeneity comprises both variations in lengths of the polypeptide backbone, "macroheterogeneity," and derivatizations of single amino acid residues, "microheterogeneity." Both types of modification govern the biological potency. The heterogeneity reflects enzymatic modifications of the primary ribosomal translation product. 3) Ubiquity. Each hormone is synthetized in different cell types, which are localized in gastrointestinal as well as extra-gastrointestinal tissues. The cell type determines the route by which the active peptide(s) reaches its target, either via blood (endocrine secretion) or by local release (neurocrine and paracrine secretion). Inasmuch as all cells contain gastrin and CCK genes, the variable expression probably reflects differentiation in development of the posttranscriptional biosynthetic machinery. 4) Differential principality. In different tissues and cells, different molecular forms may predominate. Moreover, one form is more potent with respect to one effect (e.g., CCK-8 in relation to pancreatic exocrine secretion), whereas another form (CCK-4) is more potent with respect to another effect (pancreatic endocrine secretion). Together the differential principality and secretory routes (blood borne or local) ensure that gastrin and CCK peptides regulate their targets with optimal effect in spite of the heterogeneity and wide distribution, which otherwise might cause disturbing interactions and subsequent inefficacy. The key to a better understanding of the basis characteristics is knowledge about the evolution and expression of the structural gene(s) for gastrin and CCK. Acquisition of such knowledge will be of considerable value, since available evidence suggests that the gastrin-CCK system is a good model for general features of regulatory peptides.
Hormonal regulation of canine intestinal cholesterol synthesis
Authors: Goodman M. W. , Prigge W. F. , Gebhard R. L.
Published: December 2017

Hormonal regulation of intestinal cholesterol synthesis was studied both in vitro and in vivo. Cholesterol synthesis rate was determined by measurement of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) activity and by incorporation [14C]acetate into sterol. In vitro studies utilized organ culture of canine ileal mucosa. During 6-h culture, reductase activity was stimulated sevenfold. Insulin (10-6 M) augmented this rise to 144 +/- 7% of th control activity, while 10(-8) M glucagon, 10(-3) M adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine suppressed activity (final reductase activity was 83 +/- 3%, 75 +/- 4%, and 41 +/- 3%, respectively, of cultured control values). In vivo studies utilized dogs with isolated Thiry-Vella ileal fistulas. In vivo, insulin doubled reductase activity while glucagon led to a 42 +/- 9% suppression. It is concluded that insulin and glucagon may be potential physiological regulators of intestinal cholesterol synthesis. The glucagon effect may be mediated by cyclic nucleotides.
Effect of La3+ on secretagogue-induced Ca2+ fluxes in rat isolated pancreatic acinar cells
Authors: Wakasugi H. , Stolze H. , Haase W. , Schulz I.
Published: December 2017

Addition of 0.1 mmol/l of La3+ to pancreatic acinar cells increased both the rate and extent of 45Ca+ uptake. Addition of 0.3 mmol/l La3+ did not change cellular 45Ca2+, whereas 1, 2, and 5 mmol/l gradually decreased it. If carbamylcholine (CCh) or the octapeptide of cholecystokinin-pancreozymin (CCK-OP) was added in the presence of low La3+ concentrations (0.1 and 0.3 mmol/l) to 45Ca2+-equilibrated cells, secretagogue-induced 45Ca2+ release-reuptake was not inhibited. At 1 and 2 mol/l of La3+, however, secretagogue-induced 45Ca2+ release was abolished, whereas uptake of 45Ca2+ was still increased by CCK-OP and CCh. At 5 mmol/l La3+, the effects of secretagogues were completely abolished. In the presence of 2 mmol/l La3+, the atropine-induced 45Ca2+ uptake in CCh-pretreated cells and the dibutyryl guanosine 3',5'-cyclic monophosphate-induced 45Ca2+ uptake in CCK-OP-pretreated cells were highly reduced. The data are interpreted to support our assumption that CCK-OP and CCh increase the plasma membrane permeability to Ca2+ in pancreatic acinar cells in addition to their action to initiate release of CA2+ from an intracellular Ca2+ trigger pool.
Relation between electrical and mechanical activity in esophageal smooth muscle
Authors: Goyal R. K. , Gidda J. S.
Published: December 2017

Experiments were performed in anesthetized opossums. Electrical and mechanical activity was recorded simultaneously from the esophageal body at 5, 3, and 1 cm above the lower esophageal sphincter (LES). Esophageal responses were evoked by electrical stimulation of vagal efferents or by induced swallowing. Electrical and mechanical activity was associated in 86% and dissociated in 14% of the 1,200 responses examined. The frequency of dissociation was dependent on the site in the esophagus and the frequency of vagal efferent stimulation (P less than 0.05). The interval between the onset of electrical and mechanical events, called electromechanical delay, had a regional gradient: 5 cm above LES greater than 3 cm greater than 1 cm (P less than 0.01). This delay was also dependent on the frequency of stimulation. The amplitude of spike burst and the number of spikes in a burst closely correlated with the amplitude of contraction. These studies show that electromechanical responses and dissociations are dependent on the regional level in the esophagus and the frequency of vagal stimulation.
Kinetic characteristics of calcium absorption and secretion by rat colon
Authors: Favus M. J. , Kathpalia S. C. , Coe F. L.
Published: December 2017

The kinetic characteristics of calcium active transport in rat descending colon were determined by measuring unidirectional transmural calcium fluxes in vitro. The absorptive flux from mucosa to serosa (Jm leads to s) was saturable, with a calculated affinity (Kt) of calcium for the transport system of 1.6 mM and a maximal transport capacity (Vmax) of 133 nmol.cm-2.h-1. The administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increased Jm leads to s by increasing Vmax to 236 nmol.cm-2.h-1 without changing Kt (1.8 mM). The secretory flux from serosa to mucosa (Js leads to m) was not saturable and was not increased by 1,25(OH)2D3. Mannitol, a marker of transepithelial extracellular flux, underwent net absorption in the absence of electrochemical gradients, and its Jm leads to s and Js leads to m were not altered by 1,25(OH)2D3 administration. Addition of 11 mM D-glucose to the bathing medium consistently increased calcium Js leads to m and mannitol Jm leads to s and Js leads to m. Glucose reduced net calcium absorption except when sodium was removed from the medium. Calcium Js leads to m varied linearly with mannitol Js leads to m over the range of medium calcium from 0.125 to 5.0 mM. The behavior of calcium absorption by descending colon is compatible with a carrier-mediated, active-transport mechanism, whereas calcium secretion occurs by a nonsaturable process via a predominately paracellular pathway.
Electrical control of canine jejunal propulsion
Authors: Sarr M. G. , Kelly K. A. , Gladen H. E.
Published: December 2017

We wondered whether the direction of propagation of intestinal pacesetter potentials determines the direction of movement of intestinal content. In six dogs, electrodes for pacing were implanted near each end of an 80-cm isolated jejunal loop, and a cannula was positioned at the middle of the loop for intraluminal insertion of solids and/or liquids. After recovery and during fasting, 50 nylon spheres (2 mm diam) always emptied from the distal stoma regardless of the direction of pacing. In contrast, 150 mM NaCl, given alone at 2.8 ml/min or with spheres, emptied from the distal stoma during forward pacing and from the proximal stoma during backward pacing. Spheres given with the liquid emptied from the distal stoma during forward pacing, but during backward pacing, the site of emptying varied among dogs. Neither pacing nor spheres altered jejunal interdigestive myoelectric cycles, but the perfusate abolished the cycles and resulted in a noncyclic pattern of jejunal action potentials. We concluded that the direction of pacesetter potential propagation determined the direction of liquid transit. Direction of solid transit depended, in part, on other mechanisms.
Transepithelial calcium transport by rat cecum: high-efficiency absorptive site
Authors: Nellans H. N. , Goldsmith R. S.
Published: December 2017

Transepithelial calcium transport has been investigated in rat cecum under in vitro voltage-clamp conditions. Under short-circuit conditions, the cecum behaves as a relatively tight epithelium for calcium fluxes, where mucosal-to-serosal (JCam leads to s) flux exceeds the reverse flux by at least 15-fold. JCanet is abolished in the presence of 1 mM N-ethylmaleimide, is inhibited by 40% with 1 mM ouabain, and is decreased by at least 60% when medium sodium is replaced by choline. Voltage-clamping experiments suggest that both electroneutral- and electrogenic-mediated calcium fluxes traverse the cell in the mucosal-to-serosal direction. Serosal-to-mucosal flux is purely diffusional and probably constrained to the paracellular pathway. In rats weighing less than 175 g, a low-calcium diet has no significant stimulatory effect on JCam leads to s, but a high-calcium diet markedly reduces this flux. These results suggest that the cecum possesses the highest density of calcium transport sites in the rat intestine and is ideally suited for bulk calcium absorption, which may be “down regulated” in response to an increased calcium load in growing animals.
Myoelectric properties of the cat ileocecal sphincter
Authors: Ouyang A. , Snape W. J. , Cohen S.
Published: December 2017

Myoelectric activity and intraluminal pressures were recorded simultaneously from the ileum, ileocecal sphincter (ICS), and proximal colon in chloralose-anesthetized cats. Slow-wave activity, seen at all areas, showed coupling of frequency in the distal ileum and ICS. ICS spike activity was both isolated and associated with ileal or colonic spike activity and correlated with phasic contractions (r = 0.86; P less than 0.01). Ileal distensions caused ICS relaxation and decreased spike activity 33.8% of the time. Colonic distensions caused contraction and increased spike activity 46.9% of the time. Migrating action-potential complexes (MAPC) induced by castor oil, ricinoleic acid, or cholecystokinin propagated to the ICS and through to the colon significantly more frequently than ileal non-MAPC (P less than 0.05). Both spike potential-dependent and spike potential-independent mechanisms were involved in ICS contraction. Bethanechol increased spike activity and phasic and tonic contractions. Phenylephrine, despite loss of spike activity in all leads, caused tonic contraction of the ICS. Isoproterenol caused loss of spike activity and decreased ICS pressure. Thus, ICS myoelectric activity appears to be important in determining sphincter function during neurohumoral and mechanical stimulation, with ICS contractions occurring through both a phasic spike-related mechanism and a tonic mechanism without spike activity.
Reversal of cholecystokinin-induced persistent stimulation of pancreatic enzyme secretion by dibutyryl cyclic GMP
Authors: Collins S. M. , Abdelmoumene S. , Jensen R. T. , Gardner J. D.
Published: December 2017

When pancreatic acini are first incubated with cholecystokinin, washed to remove free cholecystokinin, and then reincubated in fresh incubation solution, there is a significant residual stimulation of amylase secretion. Butyryl derivatives of cyclic GMP can prevent as well as reverse this cholecystokinin-induced residual stimulation. At 37 degrees C the nucleotide-induced reversal is complete within a few minutes, but at 4 degrees C complete reversal requires 90 min of incubation. The ability of butyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation is itself fully reversible, and the nucleotide-induced reversal is accompanied by restoration of full responsiveness to cholecystokinin. The ability of dibutyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation appears to result from the ability of the nucleotide to displace cholecystokinin from its receptors in pancreatic acini.