bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites.
Authors: Walling M W
Published: December 2017

The transport of Ca and inorganic phosphate (Pi) was studied in the absence of electrochemical gradients across rat intestine in vitro. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the active absorption of both Ca and Pi in all segments of the small intestine, with changes occurring only in absorptive fluxes, whereas secretory fluxes were unaffected. Active Ca absorption was greatest in the duodenum (greater than jejunum greater than ileum) and active Pi absorption was highest in jejunum (greater than duodenum greater than ileum), in agreement with earlier reports. 24R,25-dihydroxy-vitamin2D3 had similar effects on transport but was less potent. The ratios of Pi absorptive fluxes to Ca absorptive fluxes remained remarkably constant during 80-200% increases in absorption produced by 1,25(OH)2D3, suggesting coupled Ca-Pi transport or coordinate stimulation of Ca and Pi absorptive processes by hormonally active metabolites of vitamin D. The results seem most compatible with a differential distribution of vitamin D-responsive Ca and Pi absorptive cells with a predominance of cells with Ca absorptive sites occurring in duodenum, more Pi absorbing cells in jejunum, and a nearly equal ratio of each type in ileum.
Polarity of effects of stimulation of Auerbach's plexus on longitudinal muscle.
Authors: Yokoyama S , Ozaki T
Published: December 2017

The effects of repetitive electrical stimulation of nodes in Auerbach's plexus on the longitudinal muscle of rabbit intestine were investigated. Peeled longitudinal muscle strips, with adherent Auerbach's plexus, were obtained and placed under a stereodissecting microscope. Neural elements within nodes of Auerbach's plexus were stimulated repetitively using a metal microelectrode with tip diameter of 5 micrometer. Stimuli applied to a node generally caused excitation of the longitudinal muscle on the oral side and inhibition on the anal side of the point of stimulation. Excitation of the muscle was mainly cholinergic, and inhibition of the muscle was nonadrenergic. From the results of the present study the concept of the law of the intestine, excitation above and inhibition below the stimulated spot, was supported.
Differences in inducibility by glucocorticoids of rat liver TO and TAT.
Authors: Voigt J , Sekeris C E
Published: December 2017

The modulation of tryptophan-oxygenase (TO) and tyrosine amino-transferase (TAT) in the rat liver after a single dose of hydrocortisone has been studied under various physiological conditions. Differences in the induction behavior of the two enzymes have been observed dependent on sex, age, amount of administered hormone, and presence or absence of the adrenals. Some of the results observed are the following: 1) TO reached its maximum induction level 3 h prior to TAT in normal male rats. This difference disappeared when adrenalectomized male rats or when female animals were tested. 2) The maximal induction values of both enzymes were 50--80% higher in adrenalectomized rats than in normal rats. This effect was independent of sex. 3) Higher doses of hydrocortisone were necessary for optimal induction of TO and TAT in normal than in adrenalectomized rats. 4) The minimum dose of hydrocortisone necessary for enzyme induction was significantly lower for TO than for TAT. 5) Actinomycin D caused a complete inhibition of the induction of TO and TAT when given simultaneously with the glucocorticoid. The inhibition was less complete the longer the interval between hormone and actinomycin D administration. The activity of TAT was suppressed to a larger extent than TO.
Modeling of plasma disappearance of unlabeled insulin in man.
Authors: Tranberg K G , Dencker H
Published: December 2017

Fifty-two portal and 68 peripheral, brief infusions of unlabeled insulin were given to ambulant, nondiabetic patients. After intraportal insulin infusion (5--50 mU/kg), plasma clearance rate (PCR, dose/area of the incremental plasma insulin concentrations) decreased with increasing dose, varying from 32 to 14 ml-min-1-kg-1 at normoglycemia. After peripheral insulin infusion (5--30 mU/kg), PCR (mean value 15 ml-min-1-kg-1) showed no certain dose-dependence, but transfer rate constants and distribution volumes did. Despite a detectable reentry of insulin from one or more extravascular pools to the plasma pool, transfer rate constants or distribution volumes could not be accurately determined. The shortcomings of conventional noncompartmental and compartmental models did not appear to be due to the dose-dependence demonstrated. Instead, the limitations of these models were caused mainly by the difficulty of defining a proper base-line concentration and, in particular, by the imprecision of the experimental data, indicating that it will be difficult to find more appropriate models from data obtained with unlabeled insulin.
Synaptosomal [125I]triiodothyronine after intravenous [125I]thyroxine.
Authors: Dratman M B , Crutchfield F L
Published: December 2017

We administered [125I]thyroxine intravenously to adult male rats and measured uptake and subcellular distribution of the hormone and its metabolites in brain. Fractional brain uptake decreased after a large dose of iodothyronine, providing evidence for saturability of the uptake mechanism. Well-defined patterns of regional and subcellular labeling were noted within 1 h after [125I]thyroxine injection. Radioactivity in synaptosomes was always greater than in any other particle separated per gram of brain, increasing linearly relative to radioactivity in brain cytosol during the 1st h. Although [125I]triiodothyronine derived from [125I]thyroxine was not identified in serum at any time interval, it was measurable in synaptosomes within 20 min and in brain cytosol within 1 h after labeled hormone administration. Concentrations of the radioactive metabolite were twofold greater and ratios of [125I]triiodothyronine to [125I]thyroxine concentration were threefold greater in synaptosomes than in cytosol. Therefore, thyroxine may be converted to triiodothyronine within nerve terminals. Synaptosomal localization of iodothyronines and their metabolites may be relevant to the marked central and peripheral adrenergic nervous system effects of these aromatic amino acid hormones.
Seasonal changes in membrane lipid transitions and thyroid function in the hedgehog.
Authors: Augee M L , Raison J K , Hulbert A J
Published: December 2017

Upper (Tf) and lower (Ts) temperature limits of order-disorder transitions in blood cell lipids of hedgehogs, Erinaceus europaeus, were determined over an annual cycle. There was a significant decrease in the temperature of both Tf and Ts from values of 19 and 6 degrees C, respectively, for summer animals to values of 14 and -2.0 degrees C for winter animals. Plasma thyroxine levels decreased from a summer mean of 16.0 nmol/liter to a mean of 2.3 nmol/liter in winter. Basal oxygen consumption also decreased from the summer mean 0.45 ml/g body wt/h to a mean 0.39 ml/g body wt/h in winter. In winter a group of hedgehogs kept indoors at room temperature was compared with a group kept outdoors exposed to natural winter conditions, and there was no significant difference between them in the above parameters. We conclude that the winter membrane lipid and metabolic changes are not a response to low temperature per se but part of a circannual homeostatic adjustment at least partly regulated by thyroid hormone.
Anteroventral third ventricle lesions reduce antidiuretic responses to angiotensin II.
Authors: Bealer S L , Phillips M I , Johnson A K , Schmid P G
Published: December 2017

Ablation of anteroventral third ventricle (AV3V) periventricular tissue renders animals temporarily adipsic with no compensatory change in urine volume or concentration. The present experiment was designed to determine whether lesions of the AV3V region attenuate vasopressin (AVP) release in response to intraventricular (ivt) injections of angiotensin II (AII), hypertonic NaCl, and phenylephrine during the adipsic period. Blood pressure, urine conductance, and urine flow rate were monitored in awake, unrestrained animals during a continuous intravenous hydrating infusion. Changes in blood pressure and urine parameters were recorded following ivt injections of 100 ng AII, 500 ng AII, 1 microliter 3% NaCl, and 50 microgram phenylephrine. In addition, a radioimmunoassay (RIA) measured AVP following 500 ng AII ivt in lesioned and nonlesioned animals. Antidiuretic and pressor responses to ivt AII were attenuated after AV3V lesions. In addition, RIA analysis showed a significantly smaller concentration of AVP in lesioned animals following AII injections. These data suggest that the AV3V region is important for AVP release in response to central AII and osmotic stimuli.
Quantitative estimation of insulin sensitivity.
Authors: Bergman R N , Ider Y Z , Bowden C R , Cobelli C
Published: December 2017

We have evaluated the feasibility of using a mathematical model of glucose disappearance to estimate insulin sensitivity. Glucose was injected into conscious dogs at 100, 200, or 300 mg/kg. The measured time course of insulin was regarded as the "input," and the falling glucose concentration as the "output" of the physiological system storing and using glucose. Seven mathematical models of glucose uptake were compared to identify the representation most capable of simulating glucose disappearance. One specific nonlinear model was superior in that it 1) predicted the time course of glucose after glucose injection, 2) had four parameters that could be precisely estimated, and 3) described individual experiments with similar parameter values. Insulin sensitivity index (SI), defined as the dependence of fractional glucose disappearance on plasma insulin, was the ratio of two parameters of the chosen model and could be estimated with good reproducibility from the 300 mg/kg injection experiments (SI = 7.00 X 10(-4) +/- 24% (coefficient of variation) min-1/(microU/ml) (n = 8)). Thus, from a single glucose injection it is possible to obtain a quantitative index of insulin sensitivity that may have clinical applicability.
Effect of Krebs cycle intermediates and inhibitors on toad gastric mucosa.
Authors: Chacín J , Rincón R , Inciarte D , Cańizales A , Martínez G , Alonso D
Published: December 2017

An attempt to increase the permeability of gastric mucosa to exogenous Krebs cycle intermediates seemed advisable for a better understanding their relationship with acid secretion. At pH 7.4, citrate, oxoglutarate, fumarate, and malate had no significant effect on oxygen uptake (QO2) nor on acid secretion (QH+) by toad gastric mucosa; succinate increased QO2 slightly and had no effect on QH+; but at pH 5.0, oxoglutarate and succinate increased QO2 by 18 and 21%, respectively. 14CO2 evolved by gastric mucosa incubated with [14C]oxoglutarate, succinate, malate, or citrate was 155, 92, 128, and 353%, respectively, greater at pH 5. Citrate, oxoglutarate, succinate, fumarate, and malate increased QH+ by theophylline-stimulated mucosa at pH 5.0 by 25, 39, 35, 17 and 28%, respectively. Oxoglutarate-dependent respiration was shown to correlate with oxoglutarate oxidation. Malonate and arsenite inhibited QO2 and QH+; malonate inhibition was reversed by washout or by succinate. Arsenite was reversed by washout and accelerated by addition of lipoate immediately after washout. The results suggest that the Krebs cycle has concomitant roles in the regulation of QH+ and oxidative metabolism in the toad gastric mucosa.
Permeation of long-chain fatty acids and alcohols in rat intestine.
Authors: Sallee V L
Published: December 2017

Uptake of long-chain fatty acids and alcohols from micellar bile salt solutions has been studied with everted sacs of rat jejunum. These unidirectional uptake rates are linearly related to lipid concentration if bile salt concentration is constant, but are essentially independent of lipid concentration over a 2.5-fold concentration range if lipid and bile salt concentrations are maintained at a constant ratio. Uptake of lipid from various micellar bile salt solutions was directly related to the experimentally varied monomer activity of solute, thus allowing conversion of uptake rates to permeation coefficients. Natural logarithm of permeation coefficients (ln P) increased linearly for saturated fatty acids of 12--18 carbons, equivalent to an incremental free energy of -695 cal.mol-1 per --CH2--. Alcohols of 10- to 14-carbon chain lengths had a similar relationship on ln P to number of carbons. Previously determined permeation coefficients for fatty acids of 2--10 carbons are now seen to be a nonlinear portion of the curve for ln P versus chain length for all saturated fatty acids.
Response of Amphiuma small intestine to theophylline: effect on bicarbonate transport.
Authors: Gunter-Smith P J , White J F
Published: December 2017

The electrolyte transport properties of isolated proximal segments of Amphiuma small intestine and their response to theophylline were observed under various conditions. In the absence of theophylline the intestine generates a transepithelial potential (psi ms) serosa negative to mucosa when Cl- and HCO3- are present in the bath. Replacement of Cl- or HCO3- reduced the magnitude and usually reversed the sign of psi ms. Acetazolamide (10(-4) M) nearly abolished the serosa negative psi ms. Theophylline (10 mM) drove psi ms serosa positive, the magnitude depending on the bath Na+ and HCO3- concentrations. Simultaneously it increased the short-circuit current (Isc) and tissue resistance (Rt). The increase in Isc was not due to increase net Na+ transport in Cl-free buffer and was attributed to a residual ion flux. Acetazolamide reduced the Isc, Rt, and the net residual flux observed in theophylline-treated intestine. The magnitude of the acetazolamine effect on Isc was proportional to the Na+ and HCO3- concentrations of the bath. The results suggest that in the absence of theophylline, HCO3-, and Cl- transport are related. Furthermore, acetazolamide inhibits the movement of an ion, possibly HCO3-, secreted in response to theophylline.
No evidence for a role of reverse Na(+)-Ca2+ exchange in insulin release from mouse pancreatic islets
Authors: Garcia-Barrado M. J. , Gilon P. , Sato Y. , Nenquin M. , Henquin J. C.
Published: December 2017

We studied whether reverse Na(+)-Ca2+ exchange can increase cytoplasmic Ca2+ ([Ca2+]i) in mouse islets and contribute to insulin release. The exchange was stimulated by replacing Na+ with choline, sucrose, or lithium in a medium containing 15 mM glucose. Na+ omission increased electrical activity in B cells, [Ca2+]i, and insulin release. When voltage-dependent Ca2+ channels were blocked by nimodipine or closed by holding the membrane polarized with diazoxide, Na+ omission caused a slight hyperpolarization, a small rise in [Ca2+]i, and a marginal increase in insulin release (the latter only with choline). This small rise in [Ca2+]i was dependent on extracellular Ca2+ but was hardly augmented when intracellular Na+ was raised with alanine. When B cells were depolarized by 30 mM K+, Na+ omission did not affect the membrane potential but increased [Ca2+]i and insulin release. If Ca2+ channels were blocked by nimodipine, only marginal increases in Ca2+ and insulin release persisted, which were not different from those observed when the cells were not depolarized. This indicates that Ca2+ influx through voltage-dependent Ca2+ channels rather than via reverse Na(+)-Ca2+ exchange underlies the rise in [Ca2+]i and in insulin release produced by Na+ removal. No decisive support for Ca2+ influx by reverse Na(+)-Ca2+ exchange could be found.
Interaction between oxidative stress and gamma-linolenic acid in impaired neurovascular function of diabetic rats
Authors: Cameron N. E. , Cotter M. A.
Published: December 2017

Nerve conduction and perfusion deficits in diabetic rats depend on increased oxidative stress and impaired n-6 essential fatty acid metabolism, which are corrected by free radical scavenger and gamma-linolenic acid (GLA)-rich oil treatments, respectively. We investigated the interaction between these mechanisms on conduction velocity and endoneurial blood flow by use of low-dose antioxidant (BM15.0639) and GLA treatments, alone and in combination. After 8 wk of streptozotocin-induced diabetes, sciatic motor conduction velocity was 20.9% reduced. Treatment with GLA or BM15.0639 for the final 2 wk corrected this deficit by 18.5 and 20.0%, respectively; however, joint treatment caused 71.5% improvement, corresponding to a 7.5-fold amplification of individual drug effects. A 48.3% deficit in sciatic nutritive endoneurial blood flow was corrected by 34.8 and 24.8% with GLA and BM15.0639 treatments, respectively. With joint treatment, the flow improvement of 72.5% was greater than expected from individual drug effects, indicating a facilitatory interaction. Thus the synergistic effect of combined antioxidant and n-6 essential fatty acid treatment could potentially provide increased therapeutic power against diabetic neuropathy.
Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method
Authors: Finegood D. T. , Tzur D.
Published: December 2017

We previously demonstrated that minimal model-derived estimates of glucose effectiveness (SG), based on the frequently sampled intravenous glucose tolerance test (SGFSIGT), were reduced in islet-transplanted or streptozotocin-treated dogs and in patients with insulin-dependent diabetes mellitus. To ascertain the validity of our observations, we compared SGFSIGT with estimates based on a basal hormone replacement glucose clamp (SGBRCLAMP) and a basal hormone replacement glucose tolerance test (SGBRGTT) in normal control (CNTL, n = 12) and streptozotocin-treated dogs with normal fasting plasma glucose (STZ-Rx, n = 9). SGFSIGT was reduced in STZ-Rx compared with CNTL (P < 0.05). However, neither SGBRCLAMP nor SGBRGTT was reduced in the STZ-Rx group (P > 0.05). Comparison of protocols for each subject indicated that SGFSIGT was greater than either SGBRCLAMP or SGBRGTT in control (P < 0.002) but not in STZ-Rx dogs (P > 0.1). The relationship of SGFSIGT to insulin secretory function suggests that our previous conclusion that SGFSIGT was reduced in subjects with limited insulin release may be an artifact of the minimal-model method. Our results suggest that caution must be exercised in the interpretation of differences in minimal-model estimates of SG between subject groups with significantly different levels of insulin secretory function.
Modulation of beta-adrenergic receptor-stimulated lipolysis in the heart by prostaglandins
Authors: Ruan Y. , Kan H. , Cano C. , Malik K. U.
Published: December 2017

The purpose of the present study was to investigate the contribution of prostaglandins to lipolysis elicited by beta-adrenergic receptor activation in the heart. We have studied the effect of prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), and their precursor arachidonic acid (AA) in the presence and absence of a cyclooxygenase inhibitor, sodium meclofenamate, on glycerol output elicited by stimulation of beta-adrenergic receptors in the isolated rabbit heart with isoproterenol (ISOP). Bolus injections of ISOP (475 pmol) produced a constant increase in glycerol and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) output. Infusion of sodium meclofenamate (16 microM) reduced basal and attenuated ISOP-induced 6-keto-PGF1 alpha output and enhanced glycerol output. During inhibition of endogenous prostaglandin synthesis with meclofenamate, infusion of PGI2 or PGE2 (0.1-1 microM) inhibited ISOP-induced glycerol output. Infusion of AA (0.1-1 microM) increased 6-keto-PGF1 alpha and reduced glycerol output. Infusion of sodium meclofenamate abolished the effect of AA to increase 6-keto-PGF1 alpha and to decrease glycerol output. These data suggest that prostaglandins synthesized in the heart act as an inhibitory modulator of beta-adrenergic receptor-stimulated cardiac lipolysis.
Triacylglycerol synthesis in the different skeletal muscle fiber sections of the rat
Authors: Budohoski L. , Gorski J. , Nazar K. , Kaciuba-Uscilko H. , Terjung R. L.
Published: December 2017

Triacylglycerol (TG) synthesis rates of low-oxidative fast-twitch white and high-oxidative fast- and slow-twitch red skeletal muscle fiber sections of adult rats were measured by the incorporation of perfusate-derived palmitate into the neutral lipid fraction by use of a perfused hindquarter preparation under high-flow conditions. The perfusion medium consisted of 95% O2-5% CO2 Krebs-Henseleit buffer, pH 7.4, containing 5 g/100 ml bovine serum albumin, 100 microU/ml insulin, 5 mmol/l glucose, amino acids, and added fatty acids (FA), including 0.1 microCi/ml [3H]palmitate. FA incorporation was linear with time. TG synthesis rates correlated (r > or = 0.90) with the oxidative capacity of each of the different fiber type sections and increased in proportion to the perfusate FA concentration (0.25, 0.5, 1.0, 1.5, and 2.0 mmol/l). TG synthesis rates among different muscle fiber sections were related (r > or = 0.90) to perfusate flow during high-flow conditions; however, this was not causal, because TG synthesis rates within each muscle fiber section were independent of flow rate when experimentally varied over an approximately threefold range. Thus the relatively high TG synthesis rates observed in the high-oxidative muscle sections are not uniquely related to their high-flow capacities but are inherent to the TG synthesis process, probably events associated with FA uptake and/or capacity of the TG synthesis pathway.
Molecular and functional analysis of glutamine uptake in human hepatoma and liver-derived cells
Authors: Bode Barrie P. , Fuchs Bryan C. , Hurley Bryan P. , Conroy Jennifer L. , Suetterlin Julie E. , Tanabe Kenneth K. , Rhoads David B. , Abcouwer Steve F. , Souba Wiley W.
Published: December 2017

Human hepatoma cells take up glutamine at rates severalfold faster than the system N-mediated transport rates observed in normal human hepatocytes. Amino acid inhibition, kinetic, Northern blotting, RT-PCR, and restriction enzyme analyses collectively identified the transporter responsible in six human hepatoma cell lines as amino acid transporter B0(ATB0), the human ortholog of rodent ASCT2. The majority of glutamine uptake in liver fibroblasts and an immortalized human liver epithelial cell line (THLE-5B) was also mediated by ATB0. The 2.9-kb ATB0mRNA was equally expressed in all cell lines, whereas expression of the system A transporters ATA2 and ATA3 was variable. In contrast, the system N isoforms (SN1 and SN2) were expressed only in well-differentiated hepatomas. ATB0mRNA was also expressed in cirrhotic liver and adult and pediatric liver cancer biopsies but was not detectable in isolated human hepatocytes or fetal liver. Although the growth of all hepatomas was glutamine dependent, competitive inhibition of ATB0-mediated glutamine uptake blocked proliferation only in poorly differentiated cells lacking SN1 or SN2 expression and exhibiting low glutamine synthetase mRNA levels.
Effect of calcium on neurohumoral stimulation of feline colonic smooth muscle
Authors: Snape W. J.
Published: December 2017

The purpose of this study was to compare the effect of altering the extracellular calcium ion concentration on bethanechol or octapeptide of cholecystokinin (OP-CCK) stimulation of the isolated transverse colon of the cat. Myoelectric activity was recorded with monopolar glass-pore electrodes. Bethanechol (10(-6) M) stimulated an increase in the number of slow waves with superimposed spike potentials to 85.5 +/- 5.3% (P less than 0.001) compared with the basal spike activity (8.9 +/- 1.4%). OP-CCK (4 x 10(-9)) also increased spike activity (80.7 +/- 3.8%, P less than 0.001), which was not inhibited by atropine, phentolamine, or propranolol. Addition of 0.0 mM calcium solution to the colonic smooth muscle abolished both slow-wave and spike activity, which returned after replacing 0.25 mM calcium in the solution. Bethanechol stimulated a greater increase in spike activity as the concentration of calcium was increased. OP-CCK stimulation of colonic spike activity was more sensitive to the extracellular calcium concentration than bethanechol stimulation. Verapamil had a minimal effect on bethanechol stimulation of colonic spike activity, but it inhibited the OP-CCK stimulation. These studies suggest that 1) OP-CCK appears to stimulate colonic smooth muscle directly and 2) OP-CCK requires the presence of a greater amount of extracellular ionic calcium in order to stimulate colonic spike activity compared with bethanechol.
Mechanism of luminal alkalinization by bullfrog fundic mucosa
Authors: Takeuchi K. , Merhav A. , Silen W.
Published: December 2017

Metiamide-inhibited fundic mucosa of bullfrog secreted alkali (OH-) at 0.1-0.2 mueq.cm-2.h-1.OH- was abolished by dinitrophenol (DNP) and was decreased significantly by 4,4-didsothiocyano-2,2-disulfonate stilbene (DIDS), anoxia, or HCO3(-)-free nutrient solution. In Na+ solutions, increasing nutrient, [HCO3(-)] augmented OH- and Isc linearly while resistance (R) decreased. No such changes occurred in Na+-free nutrient solution. In all experiments, delta Isc was approximately 12 X delta OH. Replacement of Cl- in the secretory solutions or in the nutrient solutions had no significant influence on OH-. When Na+-free nutrient solutions and Cl--free secretory solutions were present, OH- decreased significantly (P less than 0.01). Increasing nutrient [Cl-] in the absence of secretory Cl- significantly (P less than 0.01) augmented OH- and Isc. In the absence of secretory Cl-, OH- and Isc were linearly related to varying nutrient [Cl-]. In tissues with nutrient solutions on the secretory side and vice versa, apparent OH- was 0.4-0.5 mueq.cm-1.h-1 and was dependent on secretory [HCO3(-)] but was not affected by DNP, DIDS, or replacement of Cl- on secretory or nutrient solutions. We conclude that 1) OH- secretion is dependent on nutrient HCO3(-) and Na+ and oxidative metabolism, 2) endogenous HCO3(-) does not contribute significantly, and 3) adequate tissue Cl- must be present for normal OH-.
Importance of food in the regulation of gastrin release and formation
Authors: Lichtenberger L. M.
Published: December 2017

This paper reviews the literature on the role of food in the homeostatic regulation of serum and tissue gastrin levels. In general, the scientific evidence indicates that, in addition to neural and systemic factors (not reviewed here), the chemical rather than the physical characteristics of a meal play an important role in the initiation of the postprandial release of gastrin. The chemical nature of those secretory stimulants have yet to be identified, and evidence is presented that pertains to the role of dietary amino acids and amines as mediators of the gastrin secretory response to a meal. The molecular events associated with food-induced gastrin release have yet to be resolved, and ultrastructural evidence is reviewed supporting three contrasting mechanisms of hormone secretion. Morphological and kinetic studies also indicate that G-cell viability and proliferation as well as intracellular gastrin formation are dependent on the oral intake of dietary stimulants of gastrin release. Additionally, evidence is presented that suggests that food may stimulate gastrin formation both acutely and chronically by catalyzing the posttranslational conversion of a precursor molecule to the active hormone and by increasing hormone biosynthesis.
Development of neurotransmitter enzyme activity in the rat gastrointestinal tract
Authors: Heitkemper M. M. , Marotta S. F.
Published: December 2017

Acetylcholine and norepinephrine play important roles in determining gastrointestinal (GI) tract motility and secretion. At this time, however, little is known concerning the postnatal developmental patterns of the enzymes that synthesize and degrade these two neurotransmitters within the GI tract. The present study examined the developmental activities, expressed per gram protein per minute, of the cholinergic enzymes choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) and the adrenergic enzymes tyrosine hydroxylase (TH) and monoamine oxidase (MAO) in male rats between days 1 and 50. Seven anatomic segments of the GI tract were assayed for enzyme activities. In general, all four neurotransmitter enzymes were present throughout the length of the GI tract and increased during the early postnatal period. The synthesizing enzymes ChAT and TH displayed peak activity prior to day 21, while the degrading enzymes AChE and MAO continued to increase past day 21. Each enzyme exhibited segmental differences and unique postnatal developmental patterns. Such differences in enzyme activities may be related to developmental increases in neuronal density, hormonal factors, or direct stimulation of the GI tract by liquid and/or solid diet.
Acute respiratory alkalosis and acidosis and rabbit intestinal ion transport in vivo
Authors: Charney A. N. , Arnold M. , Johnstone N.
Published: December 2017

The effects of acute respiratory alkalosis and acidosis on electrolyte transport in the rabbit ileum, colon, and gallbladder were studied. During in situ perfusion, anesthetized animals were ventilated with 0, 3, or 8% CO2 gas, creating states of alkalosis (pH 7.49 +/- 0.01, PCO2 = 27.0 +/- 0.9 mmHg, HCO3 = 21.7 mM), normocapnia (pH 7.38 +/- 0.02, PCO2 = 41.3 +/- 1.1 mmHg, HCO3 = 25.9 +/- 0.4 mM), and acidosis (pH 7.21 +/- 0.01, PCO2 = 66.3 +/- 1.3 mmHg, HCO3 = 28.1 +/- 0.8 mM). In the ileum alkalosis decreased the net absorption of water (-36%), sodium (-44%), and chloride (-27%), whereas acidosis had the opposite effect on water (+69%), sodium (+98%), and chloride (+32%) absorption and reduced bicarbonate secretion. Small changes in net potassium absorption occurred in the direction of water movement. There was no effect on the ileal transmural potential difference (PD). The colon and gallbladder did not respond to the acid-base disorders with changes in electrolyte transport or PD. These results suggest that systemic pH and/or PCO2 affect an electroneutral sodium chloride absorptive process in the rabbit ileum. The simple presence of this absorptive process in the gallbladder was not a sufficient basis for this organ to respond to alterations in systemic pH.
Asialoglycoprotein receptor is uninvolved in clearing intact glycoproteins from rat blood
Authors: Clarenburg R.
Published: December 2017

The hypothesis that the hepatic receptor for asialoglycoproteins would mediate turnover of glycoproteins in blood (after their desialylation by neuraminidase located on cell surfaces) was tested in rats by measuring clearance of intact 125I-labeled glycoproteins in the presence or absence of enough unlabeled asialoglycoproteins to saturate the asialoglycoprotein receptor. Via an indwelling venous catheter, a mixture of 125I-orosomucoid (obtained from rat serum) and a bolus of unlabeled asialofetuin (bovine) was injected, and infusion of an asialofetuin solution sustained. Total radioactivity and trichloroacetic acid-precipitable radioactivity were measured in blood samples taken at frequent intervals from an arterial catheter. Clearance was computer analyzed by using a two-component model. Nondestructiveness of radiolabeling and desialylation methods and interchangeability of rat and bovine (asialo)glycoproteins were demonstrated in control experiments. The infusion trials showed that independent clearance processes exist for intact and asialoglycoproteins. Apparently, the asialoglycoprotein receptor has no function in the turnover of intact plasma glycoproteins.
Neonatal intestinal oxygen consumption during arterial hypoxemia
Authors: Edelstone D. I. , Lattanzi D. R. , Paulone M. E. , Holzman I. R.
Published: December 2017

In 12 chronically catheterized neonatal lambs, we determined intestinal tract blood flow (Qi) and O2 consumption (VO2i) at O2 contents of arterial blood (CaO2) ranging from 15.3 to 3.2 ml O2/dl blood. We measured Qi with the radioactive microsphere technique and computed intestinal O2 delivery (DO2i), VO2i, and O2 extraction (VO2i/DO2i) using the Fick principle. In lambs breathing air, mean Qi = 214 ml X min-1 X 100 g intestine-1, DO2i = 27.0 ml O2 X min-1 X 100 g-1, O2 extraction = 21%, and VO2i = 5.6 ml O2 Xmin-1 X 100 g-1. During reductions in CaO2, Qi and DO2i decreased. Intestinal O2 extraction increased sufficiently, however, so that VO2i was maintained over the range of CaO2 from 15.3 to about 6.5 ml O2/dl blood. VO2i was independent of Qi at Qi greater than 160 ml X min-1 X 100 g-1. When CaO2 was reduced below values of 6.5 ml O2/dl blood, corresponding to Qi less than 160 ml X min-1 X 100 g-1, VO2i fell in association with increases in the H+ concentration difference between mesenteric venous and arterial blood. These data indicate that the intestinal tract of the neonatal lamb can meet its oxygen requirements when O2 supply varies over a wide range. When O2 availability reaches a critically low level, intestinal anaerobic metabolism develops as the O2 supply to the neonatal intestinal tract becomes inadequate for the O2 demand.
Effect of tetrodotoxin on cholinergic agonist-mediated colonic electrolyte transport
Authors: Zimmerman T. W. , Binder H. J.
Published: December 2017

Muscarinic cholinergic agonists stimulate electrolyte secretion in the intestine; nicotinic agonists augment absorption. Recent studies in rabbit ileum suggest that nicotinic but not muscarinic agonists act via an intermediary neurotransmitter. These in vitro studies in rat colon were performed to determine whether tetrodotoxin (TTX), a potent neurotoxin, inhibits cholinergic agonist-induced changes in electrolyte transport. TTX did not significantly alter basal ion transport or the ion transport changes produced by either theophylline or bethanechol, a muscarinic agonist. At a concentration of 1 mM carbachol, a mixed muscarinic-nicotinic agonist, had no apparent effect on ion transport but in the presence of TTX significantly decreased net sodium absorption, similar to the effect produced by 1 microM carbachol alone. These results are consistent with the concept that in low concentrations carbachol acts predominantly as a muscarinic agonist; in high concentrations carbachol exhibits both muscarinic and nicotinic properties that are equivalent. We conclude that muscarinic agonists alter electrolyte transport by acting directly on the enterocyte and that nicotinic agonists act indirectly by stimulating the release of an intermediary neurotransmitter.
Kinetic interpretation of hepatic multiple-indicator dilution studies
Authors: Goresky C. A.
Published: December 2017

The single-injection, multiple-indicator dilution approach, together with an analysis based on a model of microcirculatory events, provides a way of determining the composition of and the rates of processes in the liver. By comparison with a vascular reference, labeled red cells, a set of interstitial materials are found to enter the Disse space in a delayed-wave, flow-limited fashion, larger materials being excluded from a proportion of the space, and labeled water is found to undergo flow-limited distribution into the liver cells. In contrast, many other substances exhibit barrier-limited exchange with the liver cells; their tracer outflow profiles consist of throughput material (which has entered the interstitium but not the liver cells) and of returning material (which has entered the cells, later to return to the vascular space). Intracellular metabolic sequestration or biliary secretion reduces the outflow recovery of returning tracer; it also results in decreasing steady-state concentrations along sinusoids and cells and, where the cell membrane is limiting, in a step-down in concentration across it.
Influence of alpha-cellulose on myoelectric activity of proximal canine colon
Authors: Burrows C. F. , Merritt A. M.
Published: December 2017

The relations between dietary fiber intake and myoelectric activity of the proximal canine colon were examined in four normal beagles fed four diets of varying fiber content in a randomized block design. The basal diet was a canned, meat-based product to which 3, 6, and 9% by weight of alpha-cellulose was added. Colonic motility was monitored using four bipolar Ag-AgCl electrodes. Two slow-wave frequencies were observed: 1) 18.4 +/- 0.1 cycles/min (cpm) and 2) 5.6 +/- 0.03 cpm. Fiber had no effect on either frequency. Spike activity showed three distinct patterns: 1) short bursts phase locked to slow waves of the 18.4 cpm frequency, 2) short bursts phase locked to slow waves of the 5.6 cpm frequency, and 3) prolonged sequences unrelated to slow waves, lasting from 5 to greater than 60 s and grouped in distinct aborally conducted bursts that occurred at a frequency of 2.9 +/- 0.1/h (SE). Fiber had no effect on the frequency of these bursts, but as fiber intake increased there was a linear decrease in burst duration from 11.4 +/- 0.6 min for the basal diet to 8.2 +/- 0.4 min for the high-fiber diet (P less than 0.001). We conclude that luminal factors influence spike burst activity in the proximal colon, because increments of undigestible fiber reduce burst duration on a dose-related basis.
Vasopressin modulates liver regeneration in the Brattleboro rat
Authors: Russell W. E. , Bucher N. L.
Published: December 2017

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin deficiency (Brattleboro strain), both in rate of DNA synthesis and in return of liver DNA content to normal. Vasopressin treatment at physiological doses ameliorates the defect and thus appears to be an important modulator of liver regeneration in response to partial hepatectomy in the rat.
Electrical basis of contractions in the muscle layers of the pig colon
Authors: Huizinga J. D. , Diamant N. E. , El-Sharkawy T. Y.
Published: December 2017

Simultaneous in vitro measurements of electrical and mechanical activities were performed, using suction electrodes and force transducers, respectively, on longitudinal and circular muscle layers of the pig proximal colon. In addition, circular muscle strips were studied with the sucrose gap technique. Spontaneous activity was present in both preparations. In the circular muscle, slow waves with superimposed spikes occurred at a variable frequency, accompanied by phasic contractions. Longitudinal muscle preparations showed a different behavior. Regular appearance of distinct slow waves as described for the circular muscle did not occur. Instead, periods of membrane potential oscillations at a frequency of 41 cycles/min and a duration of approximately 12 s were observed in this layer. Most oscillations had superimposed spikes, and each period of oscillations was associated with a contraction. Spontaneous activity in the circular layer was myogenic in nature but susceptible to innervation and stretch. In contrast, an excitatory stimulus (acetylcholine or stretch) was a prerequisite for activity in the longitudinal layer. Cholinomimetics increased and adrenergic agents decreased the frequency of the slow waves and spiking activity and frequency and force of contractions in the circular muscle. Cholinergic agents increased the activity in the longitudinal muscle into continuous electrical oscillations with spiking activity and concomitant tonic contractile activity, whereas adrenergic agents abolished electrical and mechanical activity. Spontaneous release of acetylcholine occurred, partly due to regenerative activity of myenteric cholinergic nerves. In addition, tonic activity in the noncholinergic nonadrenergic inhibitory neurons decreased circular muscle tone.
Neurohumoral control of colonic motility in the rabbit
Authors: Snape W. J. , Shiff S.
Published: December 2017

Colonic motility was examined in the proximal (taeniated) and distal (nontaeniated) colon of New Zealand White rabbits. Colonic myoelectric and contractile activities were recorded by bipolar electrodes and extraluminal strain gauges sewn on the antimesenteric serosal surface of the proximal and distal colon. Slow-wave frequency consistently was slower in the proximal colon (13.2 +/- 0.9) compared with the distal colon (15.8 +/- 1.2) (P less than 0.05). During the control period 81.8 +/- 5.2% of slow waves have superimposed spike potentials in the proximal colon. The distal colon had similar amounts of spike activity. The distal colon had increased base-line contractility (P less than 0.02). Atropine inhibited spike and contractile activity on both sides of the colon, but the distal colon still had more contractile activity than the proximal colon (P less than 0.02). The alpha-adrenergic agonist phenylephrine and antagonist phentolamine had no effect on colonic motility. Isoproterenol inhibited colonic smooth muscle spike and contractile activity. This effect was blocked by propranolol. Administration of trimethaphan camsylate caused an increase in spike and contractile activity only in the distal colon. The effect of trimethaphan on the distal colon was inhibited by atropine. These studies show that 1) tonic cholinergic stimulation exists both in the proximal and in the distal colon, 2) circulating catecholamines have minimal effect on base-line colonic motility, and 3) tonic nonadrenergic inhibition of the distal colon modulates the tonic cholinergic stimulation.
Detection of cholecystokinin-58 in human blood by inhibition of degradation
Authors: Eberlein G. A. , Eysselein V. E. , Hesse W. H. , Goebell H. , Schaefer M. , Reeve J. R.
Published: December 2017

Although cholecystokinin-58 (CCK-58) is a major molecular form stored in the intestine, it has not yet been shown to be released into the circulation. This report describes in vitro degradation of CCK-58 in human blood and plasma and the molecular forms detected when this degradation is inhibited. After incubation of CCK-58 for 150 min between 20 and 24 degrees C, approximately 60% of immunoreactivity recovered was degraded to smaller immunoreactive forms. Storage of the 150-min incubate at -20 degrees C for 3 days greatly increased the observed degradation to 85%. When CCK-58 was added in vitro to blood, similar degradation occurred. Degradation of CCK-58 could be inhibited by addition of acid. Blood was obtained 1 h after a test meal designed to stimulate CCK release. The pH was lowered during collection and processing of blood and plasma to inhibit in vitro degradation of cholecystokinin. This method permitted the detection of significant amounts of CCK-58 in circulation.
Intracellular transport of pancreatic zymogens during caerulein supramaximal stimulation
Authors: Saito I. , Hashimoto S. , Saluja A. , Steer M. L. , Meldolesi J.
Published: December 2017

Rats infused with a dose of the secretagogue caerulein that is in excess of that which stimulates a maximal rate of pancreatic digestive enzyme secretion develop acute edematous pancreatitis. We have previously noted that infusion of this dose of caerulein (5 micrograms . kg-1 . h-1) induces the appearance of large heterogeneous vacuoles in acinar cell, blockade of exocytosis, and intracellular accumulation of digestive zymogens [O. Watanabe et al. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G457-G467, 1984 and A. Saluja et al. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G702-G710, 1985]. The current studies were performed to further elucidate these phenomena at the electron microscopic level of resolution and employed the techniques of pulse labeling, radioautography, and immunolocalization. Rats were infused with caerulein (5 micrograms . kg-1 . h-1) for 1 h, given a pulse of [3H]phenylalanine, and killed at selected times during the subsequent 5- to 180-min postpulse period during which caerulein infusion was continued. Transport from the endoplasmic reticulum to the Golgi cisternae was not altered by supramaximal stimulation, but transport through post-Golgi elements was altered. In particular, the maturation of condensing vacuoles into zymogen granules was found to be impaired. This led to the accumulation of partially condensed vacuoles and to the development of the large vacuoles containing newly synthesized digestive zymogens as well as the lysosomal hydrolase cathepsin D. The source of the latter could be impaired sorting of lysosomal and digestive enzymes and/or fusion of vacuoles with lysosomes. At the later times after pulse labeling, mature zymogen granules were also found to fuse with these large cathepsin D-containing vacuoles by a process analogous to crinophagy. Thus these studies indicate that the large heterogeneous vacuoles that appear during supramaximal secretagogue stimulation and that contain admixed digestive zymogens and lysosomal hydrolases arise by at least two mechanisms, impaired condensing vacuole maturation and crinophagy.
Differential effects of [Gln4]neurotensin on circular and longitudinal muscle of dog ileum in vitro
Authors: Karaus M. , Prasad K. R. , Sarna S. K. , Lang I. M.
Published: December 2017

We studied the effects of neurotensin analogue [Gln4]-neurotensin on isolated dog ileal longitudinal and circular muscle strips. [Gln4]neurotensin stimulated the spontaneous contractile activity of the circular muscle but inhibited that of the longitudinal muscle in a dose-dependent fashion. Hexamethonium had no effect on the spontaneous longitudinal or circular muscle contractile activity. Atropine and tetrodotoxin (TTX) both inhibited the longitudinal muscle. Atropine had no effect on the circular muscle, but TTX stimulated it. The effects of [Gln4]neurotensin on the circular muscle were reduced but not completely abolished by atropine. The inhibition of the longitudinal muscle by [Gln4]neurotensin was not reduced by any of the above antagonists but was enhanced by atropine. Electrical field stimulation (10 Hz, 100 mA) stimulated the longitudinal muscle and inhibited or stimulated the circular muscle depending on the pulse width of the stimulus. These effects were unaffected by [Gln4]neurotensin. We conclude that [Gln4]neurotensin has differential effects on isolated muscle strips of the two muscle layers in the dog ileum. It stimulates the circular muscle partially through cholinergic nerves at preganglionic sites and partially through a direct myogenic effect. [Gln4]neurotensin inhibits the spontaneous activity of the longitudinal muscle presumably by reducing the excitability of cholinergic nerves at postganglionic sites.
Effect of epidermal growth factor on growth and postnatal development of the rabbit liver
Authors: Opleta K. , O'Loughlin E. V. , Shaffer E. A. , Hayden J. , Hollenberg M. , Gall D. G.
Published: December 2017

The effect of epidermal growth factor (EGF) on the postnatal development of the liver was examined. New Zealand White rabbits received 40 micrograms.kg-1.day-1 EGF from days 3 to 17 of age either intraperitoneally or orogastrically, whereas controls received saline. At days 18-20, animals underwent cannulation of the common duct using halothane anesthetic. Biliary output was measured directly for three 1-h periods: under basal conditions and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol.min-1.kg-1, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight of intraperitoneal and orogastric groups did not differ from controls. Liver we weight, DNA, and protein content were significantly increased in intraperitoneally treated animals without morphological or biochemical evidence of fat deposition. Both intraperitoneal and orogastric EGF significantly increased bile salt secretion in the basal period and as a response to exogenous bile acid infusion. Bile flow was significantly increased in response to 1.5 mumol.min-1.kg-1 infusion of glycodeoxycholic acid. The bile salt pool was increased by both intraperitoneal and orogastric EGF. Administration of EGF resulted in a precocious development of glucokinase (EC 2.7.1.2) activity in the liver. EGF had no effect on serum cortisol, corticosterone, triiodothyronine, thyroxine, or free thyroxine levels. These findings suggest that in the neonatal period EGF can promote hepatic growth and maturation.