bluuebunny/crossref_metadata_2025 huggingface dataset:
Jejunal regulation of gastric motility patterns: effect of extrinsic neural continuity to stomach
Authors: Spencer M. P. , Sarr M. G. , Soper N. J. , Hakim N. S.
Published: December 2017

This study was designed to determine the role of extrinsic gastric innervation in mediating the inhibitory effects of jejunal infusion of mixed nutrients on canine interdigestive gastric motility patterns. Four dogs underwent transection of all extrinsic and intrinsic neural continuity to the stomach except for careful preservation of vagal innervation (stage 1). Antral manometry catheters, antral electrodes, intestinal electrodes, and a jejunal infusion catheter were placed. After a 2-wk recovery, stage 1 studies of myoelectric and contractile activity of the stomach and small bowel during fasting were recorded on four occasions during infusion of isomolar solutions of either nonnutrient NaCl (150 mM) or mixed nutrients (50% Meritene solution) into the jejunum at 2.9 ml/min for 6 h. Identical studies (stage 2) were repeated after completion of extrinsic denervation of the stomach by supradiaphragmatic vagotomy. In stage 1 studies, jejunal nutrients (83 kcal/h) inhibited the characteristic interdigestive cyclic motility patterns in the stomach and duodenum for greater than or equal to 172 min during jejunal infusion of mixed nutrients. After completion of extrinsic denervation (stage 2), jejunal infusion of nutrients had the same effects with inhibition of cyclic motility patterns in the stomach and small intestine. We concluded that inhibition of interdigestive gastric motility patterns by jejunally infused nutrients is mediated by hormonal mechanisms and not by nonvagal or vagal extrinsic neural input to the stomach.
Mechanisms of changes in K+ balance on reduction and reestablishment of flow in isolated rat liver
Authors: Sestoft L. , Folke M.
Published: December 2017

The effects of low flow and reestablished normal flow on K+ balance and carboxylic acid balance was studied in perfused liver of 48-h starved rats at perfusate pH 7.4 and 6.8. The rate of net K+ release induced by ouabain was 1.8 mumol.min-1.g-1 at pH 7.4 and 1.4 mumol.min-1.g-1 at pH 6.8. Lowering of flow to 30% normal was accompanied by a transient, diphasic loss of K+ (max 0.15 mumol.min-1.g-1). Reestablished normal flow was immediately accompanied by a monophasic K+ uptake (max 0.35 mumol.min-1.g-1). These changes in potassium balance were independent of perfusate pH. Reduction of flow caused an almost immediate depolarization of 4 mV followed by a steady tendency to repolarization. Reestablished normal flow induced a transient hyperpolarization. Production of carboxylic acids during the low flow period did not correlate with the diphasic time course of K+ loss, and carboxylic acid uptake after reestablishment of flow did not correlate with the transient uptake of K+. The data show that the initial phase of K+ loss during low flow is due to inhibition of the Na(+)-K(+)-pump; the second phase may be reasonably explained by increased K+ permeability concomitant to cellular volume regulation.
Pancreatic receptors for cholecystokinin: evidence for three receptor classes
Authors: Yu D. H. , Huang S. C. , Wank S. A. , Mantey S. , Gardner J. D. , Jensen R. T.
Published: December 2017

For inhibition of binding of 125I-Bolton-Hunter-labeled cholecystokinin octapeptide (125I-BH-CCK-8) to guinea pig pancreatic acini, the potencies for agonists were CCK-8 greater than desulfated [des(SO3)] CCK-8 greater than gastrin-17-I greater than pentagastrin greater than CCK-4 and for the antagonists L 364718 greater than proglumide analogue 10 greater than CBZ-CCK-(27-32)-NH2. For all non-sulfated agonists, the curves were biphasic with 20% of the tracer bound to sites with high affinity for these agonists with the following relative potencies: gastrin-17-I greater than pentagastrin greater than des(SO3)CCK-8 much greater than CCK-4; whereas 80% was bound to low-affinity sites with the following potencies: des(SO3)CCK-8 greater than gastrin-17-I = pentagastrin much greater than CCK-4. For L 364718 and proglumide analogue 10, 80% of 125I-BH-CCK-8 was bound to sites with high affinity for these antagonists and 20% to sites with low affinity. Analysis of the dose-inhibition curve for CCK-8 demonstrated two binding sites; however, comparison with the analysis in the presence of 0.1 microM gastrin-17-I suggested three binding sites. The gastrin-17-I dose-inhibition curve was significantly better fit by a three-site model than by a two-site model. The affinities of the various agonists and antagonists for the three sites were compared with their abilities to inhibit binding of 125I-gastrin-I and either stimulate or inhibit CCK-8-stimulated amylase release. These results demonstrate that 125I-BH-CCK-8 binds to three classes of receptors, not two as reported previously. Two classes are CCK-preferring, bind 83% of 125I-BH-CCK-8 at tracer concentrations, and comprise high- and low-affinity CCK-preferring sites that can be distinguished by all agonists but have equally high affinity for L 364718 and proglumide 10. A third class binds 17% of the tracer, cannot be differentiated from high-affinity CCK-preferring receptors by CCK-8, and has low affinities for L 364718 and proglumide 10. Future studies relating binding of 125I-BH-CCK-8 to biological activity or characterization of the CCK receptor by using radiolabeled agonists should consider CCK interaction with three receptors, not two as was done in the past.
Pharyngeal and upper esophageal sphincter manometry in humans
Authors: Castell J. A. , Dalton C. B. , Castell D. O.
Published: December 2017

Manometric studies of pharyngeal-upper esophageal sphincter (UES) coordination during swallowing have proven difficult. Asymmetry of the UES makes pressure measurements with a single, unoriented transducer suspect. Perfused systems lack the necessary response rate for measuring peak pharyngeal contraction pressures. Precise quantification of the coordination of pharyngeal contractions and UES relaxations during swallowing is difficult because of rapid pressure changes. We tested a modified solid-state transducer that measures pressures over 360 degrees. This transducer was placed in the proximal UES with a second, single transducer 5 cm proximal. Data were collected and analyzed with an Apple IIe microcomputer. A computer program was developed to measure nine timing sequences, UES resting pressure, nadir of UES relaxation, and pharyngeal contraction pressures. We studied 21 volunteers with six swallows each for dry, 5, 10, and 20 ml of water. Dry swallows differed significantly (P less than 0.05) from wet (5 ml). All timing sequences became progressively longer with increasing bolus size. Residual pressures were unchanged. Timing sequences were also measured for wet (5 ml) and dry swallows in seven volunteers using a Dent sleeve and single perfused orifice in the UES; no differences were seen.
Effect of CCK antagonist L 364718 on meal-induced pancreatic secretion in rats
Authors: O'Rourke M. F. , Reidelberger R. D. , Solomon T. E.
Published: December 2017

The specific cholecystokinin (CCK)-receptor antagonist L 364718 was used to examine the role of CCK in meal-induced pancreatic secretion. Unanesthetized rats with gastric, jugular vein, bilepancreatic, and duodenal cannulas were used; bile-pancreatic juice was recirculated. Basal amylase secretion (30% of maximal) was not inhibited by L 364718 doses of 0.5 or 2 mg/kg intravenously. L 364718 (0.02 to 2 mg/kg) caused dose-related inhibition of the maximal amylase response to CCK-8 (200 pmol.kg-1.h-1), with greater than 80% inhibition at doses greater than or equal to 0.5 mg/kg. L 364718 (0.5 mg/kg) shifted the dose-response curve to CCK-8 (25-3,200 pmol.kg-1.h-1) to the right (ED50 increased 10-fold) but did not alter maximal amylase output consistent with competitive inhibition of CCK in vivo. Ingestion of liquid food significantly increased amylase output threefold above basal. L 364718 (0.5 mg/kg) completely blocked this response. These results suggest that although CCK does not regulate basal pancreatic enzyme secretion, it is the primary mediator of pancreatic enzyme secretion in response to a liquid meal.
Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism
Authors: Pizcueta M. P. , Casamitjana R. , Bosch J. , Rodes J.
Published: December 2017

This study examined whether hyperglucagonism may promote an altered sensitivity to norepinephrine (NE) and contribute to systemic vasodilation in rats with portal hypertension due to portal vein stenosis. Three groups of male Sprague-Dawley rats were studied, portal hypertensive, normal controls, and hyperglucagonemic controls. Systemic vascular reactivity was studied by constructing dose-response curves of systemic vascular resistance (SVR) during infusions of increasing doses of NE and calculating NE ED50, the dose of NE that caused 50% of the maximal increase in SVR. Measurement of SVR was based on simultaneous measurements of arterial pressure and cardiac output (CO). Repeated measurements of CO were performed by indicator dilution curves of indocyanine green by means of a fiber-optic catheter placed in the carotid artery. Portal hypertensive rats had a decreased systemic sensitivity to NE, shown by a significant increase in NE ED50 compared with normal controls (60 +/- 8 micrograms vs. 25 +/- 3 micrograms; P less than 0.001). Glucagon levels were markedly increased in the portal hypertensive group (332 +/- 51 pg/ml vs. 176 +/- 22 pg/ml in controls; P less than 0.005). Glucagon infusion in normal rats achieved levels similar to those observed in portal hypertension (305 +/- 48 pg/ml; NS). Systemic vascular sensitivity to NE was also impaired in these hyperglucagonemic normal animals, as shown by an abnormal NE ED50 (69 +/- 16 micrograms; P less than 0.001 vs. controls) that was almost identical to that observed in portal hypertension. These results are consistent with the hypothesis that a reduced sensitivity to NE can contribute to systemic vasodilation in portal hypertension and suggest that hyperglucagonism can play a key role in its pathogenesis.
CGRP stimulates the release of pro-somatostatin-derived peptides from the gastric fundus
Authors: Bunnett N. W. , Helton W. S. , Debas H. T. , Ensinck J. W.
Published: December 2017

Calcitonin gene-related peptide (CGRP) stimulates release of peptides derived from pro-somatostatin (Pro-S) into the general circulation. The purpose of this investigation was to elucidate the origin and molecular heterogeneity of Pro-S-derived peptides secreted in response to CGRP. Catheters were placed into the vena cava and veins draining the gastric fundus and corpus, antrum, and small intestine of anesthetized pigs. Human CGRP I was infused into the descending aorta at 0.2, 0.4, 0.8, and 1.6 micrograms.kg-1.h-1 for consecutive 30-min intervals. Blood was collected from the venous catheters after each period. S-28 was separated from Pro-S, S-14, and S-13 by immunoaffinity chromatography and peptides were quantified by radioimmunoassay. CGRP primarily evoked release of peptides measured collectively as Pro-S, S-14, and S-13 into venous blood draining the fundus and corpus, and concentrations were significantly elevated above basal at 0.8 and 1.6 micrograms.kg-1.h-1 CGRP (P less than 0.05). Basal concentrations of S-28, Pro-S, S-14, and S-13 in blood from the antrum and small intestine were not significantly elevated by CGRP. In conclusion, CGRP stimulated release of Pro-S-derived peptides from the gastric fundus and corpus but not from the antrum or small intestine.
Vagal interactions on brain stem neurons receiving input from the proximal stomach in cats
Authors: Barber William D. , Yuan Chun-Su , Cammarata Brian J.
Published: December 2017

Gastric vagal fibers on the proximal stomach that join the dorsal and ventral vagal trunks were electrically stimulated to localize and evaluate brain stem neuronal interactions in anesthetized cats. The brain stem responses were located in nucleus tractus solitarius in the dorsomedial, caudal region of the medulla oblongata. There was no significant difference in the mean latency of the gastric vagally evoked brain stem response between the dorsal and ventral vagal trunks. The responses consisted of single or multiple spikes with a mean latency of ap290 ± 50 (SD) ms. Forty-one percent, or 168 unitary responses of the 406 total responses recorded, showed convergence of proximal gastric vagal input from both the dorsal and ventral vagal trunks on the same recording site or on the same cell. Of those unitary responses that received convergent proximal gastric vagal input, 95 unitary responses (57%) showed convergence of input to the same area, on different cells at the same recording site during a single trial. Seventy-three single units (43%) received convergent input from proximal gastric vagal afferent fibers in both the dorsal and ventral trunks. Fifty-two, or 7l%, of the single unit convergent responses were excitatory in nature, whereas the remaining 29% were inhibitory. These data demonstrated that proximal gastric vagal afferent fibers that join the dorsal and ventral trunks converged on a significant number of single neurons in the brain stem. The convergent response was synaptically secure and exerted an identifiable biasing effect on the response of the brain stem neuron. These convergent interactions may play an important role in reflex mechanisms concerned with adaptive relaxation to accommodate the ingested content by the proximal stomach.

gastric; proximal gastric vagal; ventral vagus; dorsal vagus; nucleus tractus solitarius; vagal brain stem interactions

Submitted on March 14, 1988

Accepted on September 19, 1989
Influence of morphine or capsaicin pretreatment on rat gastric microcirculatory response to PAF
Authors: Pique J. M. , Esplugues J. V. , Whittle B. J.
Published: December 2017

Capsaicin pretreatment, which destroys primary sensory afferent neurons, or morphine, which can inhibit peripheral sensory neurons, augments gastric damage induced by platelet-activating factor (PAF). The concurrent effects of such treatments on the changes in gastric mucosal blood flow (GMBF), as estimated by hydrogen gas clearance, and in systemic arterial blood pressure (BP) have now been determined in anesthetized rats. Intravenous infusion of PAF (25 and 50 ng.kg-1.min-1 for 30 min) induced dose-related histologically assessed mucosal damage, which was significantly potentiated by neonatal capsaicin pretreatment. Capsaicin pretreatment did not affect resting BP or GMBF or the fall in BP induced by PAF but did significantly potentiate the PAF-induced reduction in GMBF. Likewise, morphine (1.5 mg/kg iv) did not affect resting BP or GMBF or the fall in BP but did enhance the reduction in GMBF and potentiated the mucosal damage after PAF infusion; both of these effects were abolished by the opioid-antagonist naloxone (1 mg/kg iv). These findings indicate that the deleterious gastric microcirculatory changes induced by PAF are enhanced by functional ablation of sensory afferent neurons and by morphine, which may act on these neurons; these effects may therefore underlie the potentiation of gastric damage. Such local sensory neurons thus appear to be involved in the regulation of local protective microvascular responses to noxious challenge.
Myoelectric activity of small intestine after chemical ablation of myenteric neurons
Authors: Holle G. E. , Forth W.
Published: December 2017

Ablation of the myenteric plexus was performed by serosal application of 0.062% benzalkonium chloride (BAC) in the duodenum, proximal and distal jejunum, and ileum. The thickness of muscle layers and the number and sizes of ganglia and neurons of the myenteric plexus were evaluated before and 21-28 days after treatment. Electrodes were implanted on the treated segments and on segments orad and aborad to the treated segment. The electromyogram of each segment was recorded daily for periods of 2-3 h. The number of myenteric neurons in the BAC-treated segment was decreased significantly by 85 to 98% relative to segments removed before BAC application. Significantly, thickening of longitudinal plus circular muscle layers amounted to 113% in the duodenum and 261% in the ileum in the treated segment. No changes were observed in electrical slow-wave frequency in treated segments. Spike activity (percentage of slow waves with spikes) increased in the BAC-treated segment by 92% compared with recording sites orad and aborad to the treated segment and to the small intestine in untreated control animals. We interpreted the increase in spike activity in treated segments to reflect the loss of inhibitory neuronal influence. The hyperplasia and hypertrophy of the longitudinal and circular muscle coat could have resulted from a direct influence of the altered innervation or from work-induced hypertrophy in the treated segment secondary to uncoordinated hyperactivity of the disinhibited musculature.
A71378: a CCK agonist with high potency and selectivity for CCK-A receptors
Authors: Lin C. W. , Holladay M. W. , Witte D. G. , Miller T. R. , Wolfram C. A. , Bianchi B. R. , Bennett M. J. , Nadzan A. M.
Published: December 2017

Receptors for the brain and gut peptide cholecystokinin (CCK) have been classified into two classes, CCK-A and CCK-B. To date, peptide analogues with selectivity for the CCK-B receptors have been identified, and selective antagonists for CCK-A and CCK-B receptors have been reported as well; until now, there have been no reports of highly selective CCK-A agonists. Herein we describe the properties of A71378 [desamino-Try(SO3H)-Nle-Gly-Trp-Nle-(N-methyl)Asp-Phe-NH2], a highly selective CCK-A receptor ligand. Characterization of A71378 was carried out in the guinea pig pancreas, cortex, gastric gland, and ileum, as well as in NCI-H345 cells. The IC50 values of A71378 for the pancreatic CCK-A, cortical CCK-B, and gastrin receptor were 0.4 nM, 300 nM, and 1,200 nM, respectively. A71378 proved to be a potent agonist in eliciting pancreatic amylase secretion (EC50 = 0.16 nM) and ileal muscle contraction (EC50 = 3.7 nM). In contrast, A71378 was relatively weak (EC50 = 600 nM) in mobilizing intracellular calcium from NCI-H345 cells, which express CCK-B/gastrin receptors. The high potency and selectivity of A71378 for the CCK-A over CCK-B and gastrin receptors is unprecedented among CCK peptides. Studies on CCK-7 analogues indicate that N-methylation of the Asp residue is responsible for the observed selectivity for CCK-A receptors. This discovery of a selective CCK-A agonist should prove valuable for studies aimed at understanding the physiological roles of CCK-A receptors in the brain and periphery.
Base secretion in rat distal colon: ionic requirements
Authors: Feldman G. M. , Koethe J. D. , Stephenson R. L.
Published: December 2017

To evaluate the ionic requirements of colonic base secretion, segments of rat distal colon were studied under short-circuited conditions. Net base flux was composed of an active secretory component and a diffusive component. Studied in the absence of a transepithelial HCO3- concentration gradient, active base secretion was dependent on the HCO3- concentration of the bathing solution but was not influenced by the CO2 tension or pH. Base secretion appeared to saturate with a Km of 33 +/- 9 mM and was inhibited by ouabain. The diffusive component was characterized by an apparent permeability coefficient to HCO3- of 8.9 +/- 0.9 x 10(-6) cm/s. In addition to requiring HCO3- on the serosal surface, net base secretion was inhibited by reducing the Na+ concentration in the serosal medium and the Cl- concentration in the mucosal medium. These data suggest that colonic base secretion involves HCO3- entry across the basolateral surface, energized by the Na+ gradient, and HCO3- exit across the apical surface in exchange for Cl-.
Bombesin changes excitability of rat brain stem neurons sensitive to gastric distension
Authors: Ewart W. R. , Jones M. V. , Primi M. P.
Published: December 2017

The responses of single neurons in the dorsal vagal complex to physiological gastric distension were investigated in anesthetized control and capsaicin-treated rats. In both groups, the responses of brain stem neurons to close arterial injection of the regulatory peptide bombesin (BBS) were studied. These experiments observed whether selective chemical deafferentation by capsaicin caused any significant change in the central representation of responses to gastric distension and peripheral BBS administration. In 43 animals a total of 49 neurons was studied, 21 of which were in rats pretreated with capsaicin. In normal animals, the majority of neurons (89%, n = 28) responded in the same manner (increase or decrease in firing rate) to gastric distension and peripheral BBS administration. Of the 21 neurons studied in capsaicin-treated rats, 76% responded in the same direction to gastric distension and BBS. Two neurons responsive to gastric distension failed to respond to BBS. There was no significant difference between the proportion of neurons responding both to gastric distension and BBS in normal and capsaicin-treated rats. Responses to both gastric distension and BBS were abolished by bilateral cervical vagotomy in both groups of rats. In these experiments, BBS apparently acted on peripheral receptors near the stomach to produce, via the vagus nerve, effects on neuronal excitability in the dorsal vagal complex. Almost all of these neurons were also responsive to activation of gastric mechanoreceptors. The responses of dorsal vagal complex neurons to gastric distension and peripheral BBS were capsaicin insensitive, which is in contrast to the action of cholecystokinin under the same conditions.
Induction of hepatic metallothionein by intraperitoneal metal injection: an associated inflammatory response
Authors: Fleet J. C. , Golemboski K. A. , Dietert R. R. , Andrews G. K. , McCormick C. C.
Published: December 2017

The nature of hepatic metallothionein (MT) induction by several metals and its relationship to an inflammatory response was studied in chicks. Intraperitoneal (ip) injection of chromium (Cr), managanese, and iron (Fe) caused a much greater increase in hepatic MT (10.2-, 9.0-, and 6.8-fold) compared with cobalt and nickel (2.5- and 2.9-fold); thus not all transition metals are effective. Cr3+ caused markedly greater hepatic MT accumulation than Cr6+, suggesting that the ionic nature of the metal is an important factor. Small organic complexes of Fe (ferrous gluconate or lactate, 6.2-fold) caused significantly greater accumulation of hepatic MT than ferric dextran (1.4-fold), a large organic aggregate. In vitro data from chick hepatocytes and/or fibroblasts clearly indicated that Fe does not effect the induction of MT directly. The role of inflammation, as measured by recruitment of peritoneal exudate cells (PEC), was examined. Endotoxin (LPS), Sephadex (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S = Fe greater than LPS much greater than control). The percentage of heterophils but not macrophages was significantly correlated with the accumulation and induction of hepatic MT. In a similar experiment with Cr, we demonstrated that Cr3+ but not Cr6+ stimulated MT messenger RNA accumulation and concomitant hetereophil infiltration at 3 h after injection. Our results indicate that the induction of hepatic MT by the parenteral administration of a number of metals is dependent on the chemical nature of the metal and is associated with an inflammatory response.
Functionally distinct muscarinic receptors on gastric somatostatin cells
Authors: Schubert M. L. , Hightower J.
Published: December 2017

The present study was designed to examine the mode of action of muscarinic agonists on somatostatin secretion in intact gastric tissues, i.e., mucosal segments from the fundus and antrum of rat and the isolated luminally perfused mouse stomach. Methacholine caused similar decreases in somatostatin secretion in segments from the fundus (35 +/- 3%; P less than 0.001) and antrum (35 +/- 2%; P less than 0.001) of rat stomach, and in whole mouse stomach (43 +/- 3%; P less than 0.001). The decrease was the net effect of a dominant inhibition and a lesser stimulation of somatostatin secretion. Pretreatment with the permeant derivative of the acetomethoxy ester form of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM, 15 microM) caused a further decrease in methacholine-induced somatostatin secretion, implying that a stimulatory component existed that was mediated by intracellular calcium. Pretreatment with pertussis toxin (125 ng/ml) for 60 min converted the decrease in somatostatin secretion to an increase above basal levels. The increase induced by pretreatment with pertussis toxin was abolished by additional pretreatment with BAPTA/AM. Procaine (5 mM), which blocks release of calcium from intracellular stores, produced an effect on somatostatin secretion similar to that of BAPTA/AM. The results indicate that 1) methacholine exerts dual inhibitory and stimulatory effects on somatostatin cells of rat and mouse stomach, 2) the dominant effect is inhibitory and sensitive to pertussis toxin, and 3) a concurrent stimulatory effect, mediated by calcium, is unmasked after blockade of the inhibitory effect with pertussis toxin.
Role of albumin's copper binding site in copper uptake by mouse hepatocytes
Authors: McArdle H. J. , Gross S. M. , Danks D. M. , Wedd A. G.
Published: December 2017

It is possible, in vitro, to label albumin with copper either exclusively on the specific binding site or partly on the specific site and also on other sites by altering the pH at which the two ligands are mixed. Copper attached exclusively to the specific site is taken up more rapidly than copper attached to that site and others on albumin. The effect is proportional to the amount of copper on the specific site. Additional histidine stimulates uptake irrespective of the copper binding site on albumin. The effect is related to the histidine on position 3 of the albumin, since it is not seen when dog albumin is labeled under the same conditions. The data suggest that the cell recognizes and presumably binds the copper-albumin (CuAlb) complex but may preferentially recognize the ternary complex formed by CuAlb and histidine. We suggest that, in vivo, copper is bound mainly as the ternary complex and that the structure formed, presumably similar to that formed by a copper-histidine complex, is what is actually recognized by the cell. After binding, the albumin and histidine are released, possibly by a reduction step, and the copper is transported across the membrane. If the copper cannot be transported (as occurs when the cells are incubated at 4 degrees C), it blocks further binding of the ternary complex.
Contribution of intracellular calcium to gallbladder smooth muscle contraction
Authors: Renzetti L. M. , Wang M. B. , Ryan J. P.
Published: December 2017

Studies were performed to evaluate the contribution of intracellular Ca2+ to gallbladder smooth muscle contraction under acetylcholine (ACh) or potassium stimulation. Gallbladder smooth muscle strips from adult guinea pigs were placed in tissue baths containing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered physiological salt solution (PSS) and set to optimal length for contraction (Lo). The results were as follows, 1) A 20-min equilibration in zero Ca2(+)-0.1 mM ethylene glycol-bis( beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) PSS virtually abolished the response to potassium but not to ACh. 2) Substitution of strontium, an inhibitor of intracellular Ca2+ release, for Ca2+ significantly decreased the contractile response to ACh (3 X 10(-5), 10(-4), and 3 X 10(-4) M). Strontium had no effect on the response to 40 and 80 mM potassium. 3) Intracellular Ca2+ depletion significantly decreased gallbladder smooth muscle contraction to ACh (10(-4) M) but had no effect on the response to potassium (80 mM). 4) Ryanodine, a compound that inhibits Ca2+ storage by the sarcoplasmic reticulum, significantly decreased the contractile response to ACh (10(-4) M) but not to potassium (80 mM). These data support the observation that the use of intracellular Ca2+ by gallbladder smooth muscle for contraction is agonist dependent.
Responses to hypotension in conscious rats with chronic portal venous hypertension
Authors: Battarbee H. D. , Farrar G. E. , Spears R. P.
Published: December 2017

Heart rate, mean arterial pressure, and vascular conductance response to intravenous nitroprusside were compared in conscious, unrestrained portal vein-stenosed and sham-operated rats chronically instrumented for pulsed Doppler flowmetry. Ten to twelve days after portal vein stenosis, portal venous pressures were elevated and resting heart rates were greater. Portal vein-stenosed animals' depressor responses to nitroprusside were similar to those of sham-operated animals, despite a 41% reduction in their tachycardic response to arterial hypotension. Skeletal muscle vascular bed reflex responses to nitroprusside-induced hypotension were significantly attenuated in the portal vein-stenosed group, whereas their renal artery and superior mesenteric artery responses resembled that of the sham-operated group. After ganglionic blockade, tachycardic responses to hypotension were abolished, but portal vein-stenosed rats' heart rates remained greater than sham-operated rats. Comparisons of arterial pressure changes, renal artery, abdominal aorta, and superior mesenteric artery vascular conductance changes after ganglionic blockade revealed no differences in neurogenic vascular tone between groups. Ganglionic blockade enhanced nitroprusside depressor responses and increased vascular conductance responses to nitroprusside in both treatment groups while abolishing the between group difference in the skeletal muscle baroreflex response. These findings indicate that chronic prehepatic portal vein stenosis with portal venous hypertension results in reduced reflex tachycardic and skeletal muscle baroreflex responses to nitroprusside-induced hypotension.
Development of L-glutamine-stimulated electroneutral sodium absorption in piglet jejunum
Authors: Rhoads J. M. , Keku E. O. , Bennett L. E. , Quinn J. , Lecce J. G.
Published: December 2017

Glutamine is the primary metabolic fuel of the small intestine. To determine the effects of glutamine on intestinal electrolyte transport, piglet (3 days to 3 wk old) jejunum was bathed in Ussing chambers in a buffer containing 10 mM serosal glucose, and the effects of different concentrations of mucosal L-glutamine and D-glucose on short-circuit current and transmucosal Na+ and Cl- transport were measured. Resting jejunum secreted Na+ and Cl- in an electrogenic manner. In contrast to mucosal D-glucose (30 mM), which promoted electrogenic Na+ absorption (1.8 mueq.cm-2.h-1), mucosal L-glutamine (30 mM) stimulated both Na+ (2.7 mueq.cm-2.h-1) and Cl- (2.2 mueq.cm-2.h-1) absorption. This NaCl-absorptive jejunal response depended on the presence of both Na+ and Cl-, did not appear until animals were greater than 7 days of age, and was not observed with glucose, phenylalanine, or mannitol. Serosal, as well as mucosal, glutamine (30 mM) promoted electroneutral NaCl absorption. A small electrogenic Na(+)-absorptive response to L-glutamine was also observed. The effect of L-glutamine on jejunal NaCl transport resembles that of other metabolic fuels on colonic transport; its mechanism remains to be determined. We conclude that glutamine promotes electroneutral salt absorption in the small intestine.
Distinct receptors for cholecystokinin and gastrin on muscle cells of stomach and gallbladder
Authors: Grider J. R. , Makhlouf G. M.
Published: December 2017

A technique of receptor protection that enables selective preservation of one receptor type was used in conjunction with preferential antagonists of cholecystokinin (L364,718) and gastrin (L365,260) to characterize cholecystokinin (CCK) and gastrin receptors on isolated single muscle cells of the guinea pig stomach and gallbladder. In gastric muscle cells, CCK-8 and gastrin-17 were equipotent and the concentration causing 50% inhibition of response (IC50) values of both antagonists were independent of the agonist, whereas in gallbladder muscle cells, CCK-8 was more potent than gastrin-17 and the IC50 values of the antagonists were dependent on the agonist. In gastric muscle cells, CCK-8, gastrin-17, and L364,718 protected completely the response to CCK-8 or gastrin-17, and L365,260 protected partially but equally the response to both agonists. In gallbladder muscle cells, CCK-8 and L364,718 protected completely and gastrin-17 and L365,260 protected partially the response to CCK-8; conversely, gastrin-17 and L365,260 protected completely and CCK-8 and L364,718 protected partially the response to gastrin-17. The patterns of response in muscle cells from the two regions indicate the presence of one receptor type in gastric muscle cells that interacts equally with gastrin and CCK, and of two receptor types in gallbladder muscle cells, one of which interacts preferentially with CCK and the other preferentially with gastrin.
Effect of bile salt on phosphatidylcholine composition and secretion of hepatic high-density lipoproteins
Authors: Robins S. J. , Fasulo J. M. , Patton G. M.
Published: December 2017

Bile salts are necessary for the secretion of phosphatidylcholines (PCs) in bile and result in the selective secretion of highly hydrophilic molecular species of PC that contain a 16:0 acyl group. To determine the effect of bile salt on the secretion of PCs in lipoproteins, isolated rat livers were perfused with and without taurocholate. The PC composition of very-low-density lipoproteins (VLDL), newly synthesized by the liver, precisely mirrored the composition of PCs in the whole liver and was not changed with the administration of taurocholate. In contrast, both the composition of PCs in high-density lipoproteins (HDL) and the absolute amount of newly synthesized HDL were markedly affected by the administration of taurocholate. With taurocholate the PC content of HDL was increased, HDL was enriched, like bile, in 16:0 molecular species of PC, and the amount of HDL that was recovered in the perfusate was 2.5-fold greater than without taurocholate (P less than 0.001). These findings suggest that VLDL and HDL are differently derived from within the liver, that the PCs of HDL and bile originate from the same hepatic pool or by the same mechanism, and that both the secretion of bile and HDL from the liver are susceptible to regulation by bile salt.
Pacemaker activity in septal structures of canine colonic circular muscle
Authors: Ward S. M. , Sanders K. M.
Published: December 2017

Morphological and electrophysiological experiments were performed to characterize the pacemaker areas of the circular muscle in the canine proximal colon. Morphological studies showed interstitial cells of Cajal lining the submucosal surface of the circular layer and the septal structures that separate the circular layer into bundles. Electrical measurements suggested that slow waves may propagate into the thickness of the circular muscle in a regenerative manner along the surface of these septa. Removal of the submucosal pacemaker region blocked generation of slow waves in nonseptal regions of the circular muscle, but slow-wave activity continued in the circular muscle near septa. These data suggest that slow-wave pacemaker activity is not limited to a two-dimensional surface at the submucosal surface but extends into the interior of the circular layer along septal invaginations. Experiments were also performed to determine the dominance of pacemaker activity (i.e., septal vs. submucosal), and examples were found in which both areas appeared to initiate slow waves in intact muscles. Other studies showed that slow waves could propagate across septa, suggesting some form of electrical coupling between circular muscle bundles. This study provides a more complete view of the structure and function of pacemaker areas in the canine proximal colon.
Lacrimal gland inositol trisphosphate isomer and inositol tetrakisphosphate production
Authors: Dartt D. A. , Dicker D. M. , Ronco L. V. , Kjeldsen I. M. , Hodges R. R. , Murphy S. A.
Published: December 2017

In the lacrimal gland, cholinergic agonists stimulate protein and electrolyte/water secretion by producing inositol trisphosphate (IP3) from phosphatidylinositol bisphosphate. To determine which IP3 isomers were produced and whether inositol tetrakisphosphate (IP4) was produced during activation of secretion, rat exorbital gland acini were [3H]inositol-labeled and stimulated by the cholinergic agonist carbachol. Water-soluble inositol phosphates were separated by anion-exchange chromatography using Dowex columns or high-performance liquid chromatography. Intracellular Ca2+ concentration ([Ca2+]i) was measured by fluorescence using the Ca2+ dye fura-2. Carbachol (10(-3) M) produced a time-dependent increase in 1,4,5-IP3, 1,3,4-IP3, and 1,3,4,5-IP4 levels during 0-60 s of stimulation. The 1,4,5-IP3 level increased rapidly and was followed by a slower rise in 1,3,4-IP3 and 1,3,4,5-IP4 levels. A 3-s carbachol (10(-8) to 10(-2) M) stimulation caused a concentration-dependent rise in the 1,4,5-IP3 level. Carbachol (10(-9) to 10(-2) M) increased [Ca2+]i in a concentration-dependent manner. Carbachol (10(-3) M) increased [Ca2+]i to a maximum level by 10 s; by 60 s [Ca2+]i decreased by 38%. The maximum increase in 1,4,5-IP3 levels occurred at a higher carbachol concentration than the increase in [Ca2+]i or protein secretion. We concluded that cholinergic stimulation of the lacrimal gland rapidly increased 1,4,5-IP3 levels, which was responsible for the initial increase in [Ca2+]i and initial rapid phase of protein and fluid secretion. Cholinergic stimulation also increased 1,3,4-IP3 and 1,3,4,5-IP4, but more slowly; either acting alone or with 1,4,5-IP3, they could account for the slower phase of secretion.
Investigations of the migrating motor complex in domestic turkeys
Authors: Mueller L. R. , Duke G. E. , Evanson O. A.
Published: December 2017

The motor correlate of the migrating myoelectric complex (MMC) was characterized in domestic turkeys, and feeding state, age, sex, and time of day were examined as possible factors influencing the motor activity observed. Strain gauge transducers, and in a few birds Ag-AgCl bipolar electrodes, were implanted on the caudoventral thin muscle of the muscular stomach, the duodenum, ileum, cecum, and colon. Contractility was recorded for 8-10 h per bird on alternating days for 2-3 wk, except in birds involved in four 24-h recording sessions during a 2-wk period. Intense motor activity characteristic of phase III of the MMC occurred only in the ileum; other phases could not be identified. The duration, propagation velocity, and percent of cyclic motor patterns propagating from one site to another were similar to those reported in other galliform species. The occurrence of cyclic motor activity appeared to be related to food consumption; the number of motor patterns occurring during an intense feeding session was less than the number observed 1.5-2 h after feeding. In addition, more motor patterns were recorded in fasted poults during the light period than in the dark; however, the reverse was observed in juveniles fed ad libitum. Cyclic motor activity recorded in fasted 18-wk-old birds was of longer duration than that in fasted 8-wk-old birds. No statistically significant differences were noted in the cyclic motor patterns of male vs. female poults.
Characterization of beta-adrenoreceptors on smooth muscle cells from guinea pig stomach
Authors: Zhang L. , Jensen R. T. , Maton P. N.
Published: December 2017

To characterize the beta-adrenergic receptors on guinea pig gastric smooth muscle cells, we examined the effects of beta-adrenergic agonists and antagonists on biological activity, cellular adenosine 3',5'-cyclic monophosphate (cAMP), and radioligand binding. Adrenergic agonists, isoproterenol (ISO), epinephrine (EPI), and norepinephrine (NE), inhibited carbachol-stimulated contraction of muscle cells, with relative potencies (IC50S) of ISO (0.1 microM) greater than EPI (1.4 microM) greater than NE (11 microM). Each agonist increased cellular cAMP, with relative potencies (IC50S) of ISO (0.5 microM) greater than EPI (6.3 microM) greater than NE (56 microM). Binding of the nonselective beta-antagonist 125I-pindolol was temperature-dependent, saturable, reversible, and specific. 125I-pindolol binding was inhibited by the three agonists, with relative potencies (IC50S) of ISO (0.9 microM) greater than EPI (9.6 microM) greater than NE (112 microM). Pindolol inhibited binding of 125I-pindolol with an IC50 of 100 nM. The IC50 for inhibition of binding of 125I-pindolol by the relatively beta 2-selective antagonist ICI 118,551 was 70 nM and for the relatively beta 1-selective antagonist betaxolol was 1,000 nM. Computer analysis of the dose-inhibition curves for binding of 125I-pindolol for the antagonists indicated that gastric smooth muscle cells possess exclusively beta 2-adrenergic receptors of two classes, one class with a high affinity for ICI 118,551 (Kd = 50 nM) and the other with a low affinity for ICI 118,551 (Kd = 30 microM). Our results indicate that beta-adrenergic agonists interact with beta 2-adrenergic receptors on gastric smooth muscle cells to increase cellular cAMP and inhibit muscle contraction.
Volume-sensitive synaptic input to neurons in guinea pig inferior mesenteric ganglion
Authors: Anthony T. L. , Kreulen D. L.
Published: December 2017

The relationship between changes in intracolonic volume related to propulsive contractions and synaptic potentials recorded intracellularly in neurons in the inferior mesenteric ganglion (IMG) was investigated in vitro. Distension of the colon induced propulsive contractions (frequency, 2-5/min), which reduced intracolonic volume by 88%. Each propulsive contraction was sustained for 10-12 s, after which time the colon refilled. The sustained propulsive contractions were associated with a decrease in the amplitude and frequency of fast cholinergic excitatory postsynaptic potentials (EPSPs) and partial repolarization of the slow EPSP. The pressure-volume relationships of the colonic segments had two limbs: at distension pressures less than 15 cmH2O ("volume limb") the intracolonic volume was proportional to the distension pressure; greater than 15 cmH2O ("pressure limb") the intracolonic volume did not increase further. The changes in synaptic input were related to these pressure-volume relationships. In the volume limb, the frequency and amplitude of fast EPSPs were proportional to intracolonic volume and maximized with volume. In the pressure limb, there was a slow depolarization of the membrane that increased with greater distension pressures. Under isovolumic conditions, the changes in intraluminal pressure associated with colonic contractions were not associated with changes in excitatory synaptic input to IMG neurons. These experiments demonstrate that colonic mechanoreceptors to IMG neurons are sensitive to both intracolonic volume and pressure.
Luminal polyamines stimulate repair of gastric mucosal stress ulcers
Authors: Wang J. Y. , Johnson L. R.
Published: December 2017

The purpose of this study was to examine whether luminal polyamines can substitute for tissue polyamines in the healing process of gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately or at 4, 12, or 24 h after the period of stress. Stress significantly increased ornithine decarboxylase (ODC) activity and tissue polyamine content. Mucosal polyamine levels peaked 4 h after stress and remained significantly elevated for 12 h. The healing process, which was significant by 12 h, was inhibited by DL-alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC. DFMO totally prevented the marked increases in ODC and polyamine levels that usually followed stress. Oral administration of polyamines, putrescine, cadaverine, spermidine, or spermine, immediately after stress increased the normal rate of healing and prevented the inhibition of repair caused by DFMO. Spermidine or spermine accelerated healing better than putrescine or cadaverine. The delayed recovery of mucosal DNA, RNA, and protein content after stress in the DFMO-treated rats was also significantly prevented by exogenous polyamines. The reduced amounts of gastric mucosal spermidine and spermine in rats treated with DFMO returned toward control levels after administration of exogenous spermidine (100 mg/kg). These results show that 1) increased levels of polyamines provided by ODC are absolutely required for normal healing of gastric mucosal stress ulcers, 2) the polyamines are active from the luminal side, and 3) polyamines accelerate healing at least partly through a mechanism involving cell renewal.
Both tissue and serum phospholipases release rat intestinal alkaline phosphatase
Authors: Eliakim R. , Becich M. J. , Green K. , Alpers D. H.
Published: December 2017

Rat intestinal alkaline phosphatase (IAP) is unique among the brush-border membrane enzymes in that it is released bidirectionally (lumen and blood) and exists in either soluble (serum) or particulate (cellular) form. To elucidate the mechanism of membrane release, we examined the effects of phosphatidylinositol-specific phospholipase C (PtdIns-PLC) and serum anchor-specific phospholipase D (PLD) on the solubility of the various tissue forms of IAP. The "solubility" of cytosol IAP could be explained in part by intracellular PtdIns-PLC activity, detected by production of acidic IAP isomers, and by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)-sensitive PtdIns hydrolysis. Contamination with serum (abundant with anchor-specific PLD) was responsible for the complete or partial solubilization of IAP that was found during processing of light mucosal scrapings. Anchor-specific PLD activity was increased after fat feeding, and the IAP released did not react with antiserum that recognizes the PtdIns-PLC-released phospholipid portion of trypanosomal variable surface glycoprotein. These data are consistent with the hypothesis that, after secretion from the enterocyte bound to a phospholipid-rich membranous particle, IAP release into serum is mediated by serum anchor-specific PLD. The soluble forms of IAP in the lumen and the cytosol fraction appear to be due to a combination of endogenous PtdIns-PLC activity and anchor-specific PLD contamination that occurs during cell fractionation.