bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of ingestive behavior
Authors: Ross Michael G. , Nijland Mark J. M.
Published: December 2017

Swallowing represents a primary physiological function that provides for the ingestion of food and fluid. In precocial species, swallowing activity likely develops in utero to provide for a functional system during the neonatal period. The chronically instrumented ovine fetal preparation has provided the opportunity for recent advances in understanding the regulation of in utero swallowing activity. The near-term ovine fetus swallows fluid volumes (100–300 ml/kg) that are markedly greater, per body weight, than that of the adult (40–60 ml/kg). Spontaneous in utero swallowing and ingestive behavior contribute importantly to the regulation of amniotic fluid volume and composition, the acquisition and potential recirculation of solutes from the fetal environment, and the maturation of the fetal gastrointestinal tract. Fetal swallowing activity is influenced by fetal maturation, neurobehavioral state alterations, and the volume of amniotic fluid. Furthermore, intact dipsogenic mechanisms (osmolality, angiotensin II) have been demonstrated in the near-term ovine fetus. It remains unknown to what degree, if any, fetal swallowing may be influenced by nutrient appetite, salt appetite, or taste. Nevertheless, the development of dipsogenic and additional regulatory mechanisms for ingestive behavior occurs during fetal life and may be susceptible to changes in the pregnancy environment. This review describes what is currently known regarding the in utero development of ingestive behavior and the importance of this activity for fetal and perhaps ultimately adult fluid homeostasis.
IGF-I alters lymphocyte survival and regeneration in thymus and spleen after dexamethasone treatment
Authors: Hinton Pamela S. , Peterson Catherine A. , Dahly Elizabeth M. , Ney Denise M.
Published: December 2017

Insulin-like growth factor I (IGF-I) is a growth factor for the immune system, increasing lymphocyte number and function via greater lymphocyte generation and/or survival. We investigated the effects of IGF-I on lymphocyte survival and regeneration in the thymus and spleen after dexamethasone (Dex) treatment in rats maintained with parenteral nutrition and given recombinant human IGF-I (800 μg/day) for 12 h, 48 h, and 5 days. IGF-I did not prevent Dex-induced apoptosis of thymocytes but reduced cell death in the spleen at 12 and 48 h. IGF-I exerted a modest protective effect (10–15% reduction in cell loss) on all splenic T and B cell subsets examined by flow cytometry. IGF-I enhanced recovery of CD4+8+ immature T cells in the thymus and decreased the proportion of CD8+ (cytotoxic/suppressor) T cells in the spleen. In rats not treated with Dex, IGF-I significantly increased total lymphocyte number and the number of CD4+8+ T cells in thymus and spleen. Our results suggest that IGF-I may alter homeostasis in the immune system by modulating lymphocyte generation and survival.
Splanchnic and vagal denervation attenuate central Fos but not AVP responses to intragastric salt in rats
Authors: Carlson Scott H. , Osborn John W.
Published: December 2017

We have recently reported that an acute intragastric hypertonic saline load increases plasma arginine vasopressin (PAVP) and Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We hypothesized that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and/or vagal afferent projections. To test this hypothesis, we examined the effect of bilateral subdiaphragmatic vagotomy and bilateral splanchnic denervation on the PAVP and Fos immunoreactivity responses to intragastric hypertonic saline infusion in awake rats. Compared with responses in sham rats, Fos immunoreactivity responses were significantly reduced in vagotomized rats in the AP, SON, and PVN, whereas normal Fos levels were observed in the LPBN. However, vagotomized rats exhibited a normal increase in PAVP. Splanchnic-denervated rats also exhibited similar changes in PAVP in response to intragastric hypertonic saline compared with sham-denervated rats, and no differences were observed in Fos immunoreactivity in the LPBN, SON, and PVN compared with sham rats. However, splanchnic-denervated rats were observed to have significantly lower Fos staining in the NTS and AP compared with sham rats. The inability of splanchnic or vagal denervation alone to block the PAVP response to intragastric hypertonic saline suggests that either peripheral osmoreceptors project via both splanchnic and vagal afferents to mediate AVP release or that the observed response of PAVP is due to the activation of central osmoreceptors in the absence of measurable changes in plasma osmolality.
Delayed vagal withdrawal slows circulatory but not oxygen uptake responses at work increase
Authors: Hayashi Naoyuki , Tanaka Ayumu , Ishihara Mutsuhisa , Yoshida Takayoshi
Published: December 2017

The effect of delayed vagal activity withdrawal on cardiorespiratory responses at an increase in workload was examined. Eleven volunteers (21 ± 3 yr, 66 ± 4 kg) performed cycle ergometer exercise at a work rate corresponding to 80% of ventilatory threshold after 3 min of unloaded cycling. Facial stimulation was given by applying a vinyl bag filled with cold water (3–5°C) to the face 1 min before to 1 min after the increase in workload (S2 trial) or no stimulation was given (Nr trial). Oxygen uptake (V˙o 2), heart rate (HR), and cardiac output (Q˙) were continuously recorded in four transitions for each trial. Data were averaged for each subject and trial. Mean response time (MRT, sum of delay and time constant) was calculated with a monoexponential fitting. Facial stimulation induced acute bradycardia (−10 ± 5 beats/min in S2 trial). The MRT of HR and Q˙ was significantly longer in the S2 trials (46 ± 35 and 37 ± 23 s) than in the Nr trials (26 ± 18 and 28 ± 19 s, respectively), but no significant change inV˙o 2 MRT was shown (36 ± 7 vs. 38 ± 12 s). These findings suggest that increased vagal activity delays the central circulatory responses, which does not alter the V˙o 2 kinetics at the onset of stepwise increase in workload. The maintenance ofV˙o 2 kinetics during acute bradycardia may either reflect the fact that some intramuscular processes (such as oxidative enzyme inertia) limitV˙o 2 kinetics or alternatively that increased sympathetic vasoconstriction at some remote site defends exercising muscle blood flow.
Persistence of metabolic rhythmicity during fasting and its entrainment by restricted feeding schedules in rats
Authors: Escobar Carolina , Díaz-Muñoz Mauricio , Encinas Fabiola , Aguilar-Roblero Raúl
Published: December 2017

The presence of a food-entrainable oscillator (FEO) independent from the SCN is now well established, but until now its location and characterization have been elusive. Because its expression requires priming of the animal’s metabolism toward a catabolic state, it is possible that metabolic rhythms may be related to FEO. The present study was designed to determine whether metabolic rhythms persist during fasting and whether such rhythms could be entrained to a restricted feeding schedule. The results indicate persistent rhythms of triacylglycerides, free fatty acids, glucose, and proteins during fasting, whereas ketone bodies and liver glycogen changed their concentration as a function of fasting. Daily food pulses of 2 h entrained the rhythms of triacylglycerides and free fatty acids and restored ketone bodies and liver glycogen to similar levels as controls. Neither glucose nor proteins were affected by the food pulse. These results indicate the relevance of lipid metabolism as a phenomenon associated with the FEO.
NO modulates fetoplacental blood flow distribution and whole body oxygen extraction in fetal sheep
Authors: Smolich Joseph J.
Published: December 2017

It is unknown if nitric oxide (NO) influences the relative level of the left (LV) and right ventricular (RV) outputs, the blood flow distribution between the body and placenta, or whole body O2extraction and O2consumption in the fetus. To address these questions eight fetal lambs were chronically instrumented at 128–134 days gestation (term 147 days), and blood flows were measured with radioactive microspheres 3–4 days later at baseline and after inhibition of NO synthesis with Nω-nitro-l-arginine (l-NNA, 10 and 25 mg/kg iv).l-NNA progressively reduced the combined ventricular output ( P < 0.005) but did not alter the relative levels of the LV and RV outputs. Fetal body blood flow fell by 31% after 10 mg/kgl-NNA ( P < 0.005), but a reduction in placental blood flow ( P < 0.005) was smaller (20%) and not observed until 25 mg/kgl-NNA. Whole body O2extraction increased by 71% after 10 mg/kg l-NNA ( P < 0.005) and did change further at 25 mg/kg l-NNA, whereas whole body O2consumption rose by 15% at 10 mg/kg l-NNA ( P < 0.05) and returned to baseline at 25 mg/kg l-NNA. These results suggest that, as well as reducing the combined ventricular output, inhibition of fetal NO synthesis redistributes systemic blood flow toward the placenta and increases fetal body O2extraction. The latter initially increases whole body O2consumption and then maintains it at near baseline levels after a fall in placental perfusion.
Thromboxane A2 acts on the brain to mediate hemodynamic, adrenocorticotropin, and cortisol responses
Authors: Cudd Timothy A.
Published: December 2017

Conditions that increase the formation of thromboxane A2(TxA2) also result in activation of hemodynamic and adrenocortical responses. The purpose of this study was to test the hypothesis that TxA2 acts directly on the brain to mediate these responses. Adult sheep were chronically instrumented with vascular and intracerebroventricular catheters. The TxA2 analog U-46619 (0, 100, or 1,000 ng ⋅ kg−1 ⋅ min−1) and artificial cerebrospinal fluid (CSF) were infused intracerebroventricularly for 30 min. Heart rate increased in response to 100 ng ⋅ kg−1 ⋅ min−1U-46619 infusions. Heart rate did not change over preinfusion values in response to the highest infusion rate, but values were elevated compared with the postinfusion period. Mean arterial pressure, ACTH, cortisol, hematocrit, and arterial pH (pHa) increased, and arterial partial CO2 pressure ([Formula: see text]) fell in response to 1,000 ng ⋅ kg−1 ⋅ min−1infusions of U-46619. Plasma vasopressin concentrations and arterial partial O2 pressure did not change. In a second study, U-46619 or artificial CSF was infused intracerebroventricularly during prostaglandin synthase blockade. Blockade reduced but did not prevent blood pressure responses to U-46619 infusion, suggesting that the U-46619 infusions increased prostaglandin synthase metabolism to contribute de novo TxA2 or a second metabolite to augment the blood pressure response. Heart rate, pHa,[Formula: see text], ACTH, and cortisol responses to U-46619 were not different with blockade. We conclude that TxA2 acts on the brain to mediate blood pressure, heart rate, pHa,[Formula: see text], hematocrit, ACTH, and cortisol responses. These findings support the hypothesis that TxA2 acts directly on the brain to promote cardiovascular and hormonal responses that may serve a protective function during conditions when TxA2 formation is increased.
K+-neutral amino acid symport ofBombyx morilarval midgut: a system operative in extreme conditions
Authors: Giordana B. , Leonardi M. G. , Casartelli M. , Consonni P. , Parenti P.
Published: December 2017

The K+-dependent symporter for leucine and other neutral amino acids expressed along the midgut of the silkworm Bombyx mori operates with best efficiency in the presence of a steep pH gradient across the brush-border membrane, with external alkaline pH values up to 11, and an electrical potential difference (Δψ) of ∼200 mV. Careful determinations of leucine kinetics as a function of external amino acid concentrations between 50 and 1,000 μM, performed with brush-border membrane vesicles (BBMV) obtained from the middle and posterior midgut regions, revealed that the kinetic parameter affected by the presence of a ΔpH was the maximal rate of transport. The addition of Δψ caused a further marked increase of the translocation rate. At nonsaturating leucine concentrations in the solution bathing the external side of the brush-border membrane, leucine accumulation within BBMV and midgut cells was not only driven by the gradient of the driver cation K+and Δψ but occurred also in the absence of K+. The ability of the symporter to translocate the substrate in its binary form allows the intracellular accumulation of leucine in the absence of K+, provided that a pH gradient, with alkaline outside, is present. The mechanisms involved in this accumulation are discussed.
Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction
Authors: Timmons James A. , Poucher Simon M. , Constantin-Teodosiu Dumitru , Macdonald Ian A. , Greenhaff Paul L.
Published: December 2017

Pyruvate dehydrogenase complex (PDC) activation status has been described as being central in the regulation of tissue substrate oxidation as outlined by the glucose fatty-acid cycle. In the present study we examined the effects of reduced lipolysis, with use of nicotinate, and increased PDC activation, with use of dichloroacetate (DCA), on substrate utilization during 20 min of submaximal steady-state contraction (∼80% of maximal O2uptake) in canine gracilis skeletal muscle. At rest, PDC activation was unchanged by nicotinate but was ∼2.5-fold higher in the DCA group than in the control group ( P < 0.05). During contraction, PDC activation status increased to 3.5 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the control group, remained at 4.5 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the DCA group, but only increased to 2.2 mmol acetyl-CoA ⋅ min−1 ⋅ kg−1at 37°C in the nicotinate group ( P< 0.05). However, the estimated amount of carbohydrate oxidized during the 20-min contraction was similar across groups and did not follow the degree of PDC activation (81.2 ± 22.9, 95.9 ± 11.7, and 89.3 ± 18.9 mmol glucosyl units/kg dry muscle for control, nicotinate, and DCA, respectively). Thus it would appear that, during steady-state contraction, PDC activation status does not determine the rate of carbohydrate oxidation in skeletal muscle.
A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2αon retinal vessels
Authors: Lahaie Isabelle , Hardy Pierre , Hou Xin , Hasséssian Haroutioun , Asselin Pierre , Lachapelle Pierre , Almazan Guillermina , Varma Daya R. , Morrow Jason D. , Roberts L. Jackson , Chemtob Sylvain
Published: December 2017

Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F2α(8-iso-PGF2α) on retinal vasculature from piglets. 8-Iso-PGF2αpotently contracted (EC50= 5.9 ± 0.5 nM) retinal vessels. These effects were completely antagonized by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane receptor antagonist L-670596, and the putative inhibitor of the non-voltage-dependent receptor-operated Ca2+pathway SKF-96365; constrictor effects of 8-iso-PGF2αwere also partly attenuated by the ETA-receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca2+channel blocker nifedipine. Correspondingly, 8-iso-PGF2αelicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2αalso increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2αwere blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF2αalso increased Ca2+transients in retinal endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2α, stimulated a rise in Ca2+transients. Finally, H2O2+ FeCl2(in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2αin the retina. In conclusion, 8-iso-PGF2α-induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca2+entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.
Vagovagal reflex motility patterns of the rat esophagus
Authors: Lu Wei Yang , Bieger Detlef
Published: December 2017

Esophageal reflex motility and its neural correlates were investigated in 94 urethan-anesthetized adult male albino rats. When distended by means of a stationary balloon, the cervical and thoracic esophageal portion responded with a single pressure wave (type I response), whereas the diaphragmatic (intercrural) segment exhibited rhythmic contractions (type II response). Balloon deflation resulted in an off response aboral to the balloon. Bilateral cervical vagotomy or systemicd-tubocurarine abolished all types of reflex responses. Both type I and type II responses were associated with multiunit discharges in the central subnucleus of the solitary tract complex (NTSC) and the compact formation of the nucleus ambiguus (AMBC). Type I discharges, consisting of single bursts, and type II discharges, consisting of rhythmic 0.6-Hz bursts, preceded intraesophageal pressure waves in a fixed phase relationship, persisted after contralateral vagotomy, and were eliminated by ipsilateral vagotomy. During neuromuscular paralysis, peak intraburst discharge rates were reduced in both the NTSC and AMBC, with a concomitant decrease in rhythmicity. It is concluded that bolus-evoked peristalsis of the rat esophagus is 1) segmentally organized; 2) effected by a bilateral uncrossed reflex arc consisting of vagal viscerosensory, NTSC premotor, and AMBC motoneurons innervating the striated muscle tunic and 3) strongly facilitated by reafferent feedback.
Vagal afferent transmission in the NTS mediating reflex responses of the rat esophagus
Authors: Lu Wei Yang , Bieger Detlef
Published: December 2017

In urethan-anesthetized rats, esophageal distension evoked volume-dependent reflex contractions with phase-locked multiunit discharges in the central subnucleus of the solitary tract complex (NTSC) and the nucleus ambiguus. During blockade of solitarial, but not peripheral, muscarinic cholinoceptors, the volume-response relationship of reflex contractions was shifted rightward with a depression in pressure wave amplitude. Concurrently, premotor NTSCresponses were attenuated and nucleus ambiguus activity was abolished during esophagomotor inhibition. Both NTSC discharges and reflex responses were eliminated, or strongly inhibited, during blockade of excitatory amino acid receptors (EAARs) with 6-cyano-7-nitroquinoxaline-2,3-dione, γ-glutamylglycine or 2-amino-7-phosphonoheptanoate. In brain stem slice preparations, whole cell recordings in the NTSC region revealed fast excitatory postsynaptic potentials (EPSPs) with spikes in response to electrical stimulation of the solitary tract. Although spiking was facilitated by muscarine, EPSPs were resistant to cholinoceptor antagonists but sensitive to EAAR blockers. We conclude that esophageal vagal afferents excite ipsilateral NTSC interneurons via activation of glutamate receptors of thedl-α-amino-3-hydroxy-5-methylisoxazole-propionic acid and N-methyl-d-aspartate subtypes. Cholinergic input to the NTSC probably derives from propriobulbar sources and serves to modulate the responsiveness of reflex interneurons.
Sphingomyelinase has an insulin-like effect on glucose transporter translocation in adipocytes
Authors: David T. S. , Ortiz P. A. , Smith T. R. , Turinsky J.
Published: December 2017

Rat epididymal adipocytes were incubated with 0, 0.1, and 1 mU sphingomyelinase/ml for 30 or 60 min, and glucose uptake and GLUT-1 and GLUT-4 translocation were assessed. Adipocytes exposed to 1 mU sphingomyelinase/ml exhibited a 173% increase in glucose uptake. Sphingomyelinase had no effect on the abundance of GLUT-1 in the plasma membrane of adipocytes. In contrast, 1 mU sphingomyelinase/ml increased plasma membrane content of GLUT-4 by 120% and produced a simultaneous decrease in GLUT-4 abundance in the low-density microsomal fraction. Sphingomyelinase had no effect on tyrosine phosphorylation of either the insulin receptor β-subunit or the insulin receptor substrate-1, a signaling molecule in the insulin signaling pathway. It is concluded that the incubation of adipocytes with sphingomyelinase results in insulin-like translocation of GLUT-4 to the plasma membrane and that this translocation does not occur via the activation of the initial components of the insulin signaling pathway.
Leptin depolarizes rat hypothalamic paraventricular nucleus neurons
Authors: Powis Jeff E. , Bains Jaideep S. , Ferguson Alastair V.
Published: December 2017

Leptin, the protein product of the ob/ obgene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. The paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22–56) elicited dose-related depolarizations in 82% of the type I cells tested ( n = 17) and 67% of the type II cells tested ( n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57–92) had no discernible effect on membrane potential ( n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin ( n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near −30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.
Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting
Authors: Kaibara Atsushi , Moshyedi Armin , Auffenberg Troy , Abouhamze Amer , Copeland Edward M. , Kalra Satya , Moldawer Lyle L.
Published: December 2017

The ob gene product leptin is known to produce anorexia and loss of body fat when chronically administered to both lean and genetically obese mice. The current study was undertaken to examine whether administration of recombinant leptin in quantities sufficient to produce decreases in food intake and body weight and alterations in body composition would elicit either an hepatic acute phase protein response or preferential loss of carcass lean tissue. Mice were administered increasing quantities of recombinant human leptin or human tumor necrosis factor-α as a positive control. Although leptin (at 10 mg/kg body wt) produced significant anorexia and weight loss (both P < 0.05), human leptin administration did not appear to induce an hepatic acute phase protein response in either lean or genetically obese mice, as determined by protein synthetic rates in the liver or changes in the plasma concentration of the murine acute phase protein reactants, amyloid A, amyloid P, or seromucoid (α1-acid glycoprotein). In addition, human leptin administration did not induce a loss of fat-free dry mass (protein) in lean or obese animals. The findings suggest that at doses adequate to alter food intake and body weight leptin is not a significant inducer of the hepatic acute phase response nor does leptin promote the preferential loss of somatic protein characteristic of a chronic inflammatory process.
Catecholamines inhibit growth in fetal sheep in the absence of hypoxemia
Authors: Bassett John M. , Hanson Clifford
Published: December 2017

To evaluate contributions of catecholamines to inhibition of growth during chronic hypoxemia or severe undernutrition, epinephrine (Epi; 0.25–0.35 μg ⋅ kg−1 ⋅ min−1) or norepinephrine (NE; 0.5–0.7 μg ⋅ kg−1 ⋅ min−1) was administered to normoxemic fetuses in twin-pregnant ewes for 8–12 days, from 125 to 127 days of gestation. Both had similar effects and decreased fetal weight by ∼20% relative to control twins ( P < 0.01). Weight gain ceased during infusion of Epi or NE (−21 ± 14.8 or 14 ± 20.9 g/day), whereas controls gained 93 ± 13.2 g/day ( P < 0.01). Effects on tissues and organs varied, spleen and thymus being most retarded, whereas brain weight and skeletal measures were affected little. Selected muscles from infused fetuses weighed 72% of those in controls. Growth ceased during infusion ( P < 0.001). Weight gain of hindlimb bones was negligible, but length increased at 56% of control rates. Arterial blood CO2and plasma insulin were decreased ( P< 0.001), but plasma glucose, growth hormone, and blood oxygenation increased ( P < 0.001). Actions of Epi and NE could underlie asymmetrical growth retardation occurring in many adverse physiological situations during fetal development.
Impact of starvation-refeeding on kinetics and protein expression of trout liver NADPH-production systems
Authors: Barroso Juan B. , Peragón Juan , Contreras-Jurado Constanza , García-Salguero Leticia , Corpas Francisco J. , Esteban Francisco J. , Peinado María A. , De La Higuera Manuel , Lupiáñez José A.
Published: December 2017

Herein we report on the kinetic and protein expression of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase, and malic enzyme (ME) in the liver of the trout ( Oncorhynchus mykiss) during a long-term starvation-refeeding cycle. Starvation significantly depressed the activity of these enzymes by almost 60%, without changing the Michaelis constant. The time response to this nutritional stimulus increased with fish weight. The sharp decline in G6PDH and ME activities was due to a specific protein-repression phenomenon, as demonstrated by molecular and immunohistochemical analyses. Also, the dimeric banding pattern of liver G6PDH shifted from the fully reduced and partially oxidized forms, predominant in control, to a fully oxidized form, more sensitive to proteolytic inactivation. Refeeding caused opposite effects in both protein concentration and enzyme activities of about twice the control values in the first stages, later reaching the normal enzyme activity levels. Additionally, the partially oxidized form of G6PDH increased. The kinetics of these enzymes were examined in relation to the various metabolic roles of NADPH. These results clearly indicate that trout liver undergoes protein repression-induction processes under these two contrasting nutritional conditions.
Gastric volume detection after selective vagotomies in rats
Authors: Phillips Robert J. , Powley Terry L.
Published: December 2017

Rats receiving intragastric infusions of 2.5, 5.0, 7.5, or 10.0 ml of normal saline while their pylori are reversibly occluded suppress meal size to the smallest infusion and display a dose-dependent reduction across volumes [Phillips, R. J., and T. L. Powley. Am. J. Physiol. 271 ( Regulatory Integrative Comp. Physiol.40): R766–R779, 1996]. To evaluate the contributions of the vagus to this detection of gastric volume, groups prepared with different selective vagotomies and equipped with pyloric cuffs and gastric catheters were tested. Liquid diet consumption during a 30-min feeding bout was measured after infusions of 5.0 and 10.0 ml of normal saline on cuff-open and cuff-closed trials. Consistent with earlier observations, sham animals with cuffs closed exhibited volume-dependent suppression of food intake to the infusions, and completely vagotomized animals did not inhibit feeding in response to the loads. In cuff-closed trials, the suppression function slopes of the selective vagotomy groups were intermediate to those of the shams and the completely vagotomized animals. Furthermore, for the different groups, the extent of suppression after vagotomy was proportional to the density of the afferent innervation respective branches supplied to the stomach. Specifically, the group with the gastric branches spared (nonsignificantly attenuated in comparison to shams) and the group with only the hepatic branch spared (significantly attenuated with respect to shams) both still exhibited significant dose-dependent suppression slopes (compared with completes), whereas the group with only celiac branches spared was not significantly different from completely vagotomized animals. In sum, the vagus nerve mediates the detection of the gastric volumes tested, and the different branches of the vagus make distinctive contributions to this afferent feedback.
In birds, NHE2 is major brush-border Na+/H+exchanger in colon and is increased by a low-NaCl diet
Authors: Donowitz M. , De La Horra C. , Calonge M. L. , Wood I. S. , Dyer J. , Gribble S. M. , De Medina F. Sanchez , Tse C. M. , Shirazi-Beechey S. P. , Ilundain A. A.
Published: December 2017

We previously reported that mammalian small intestinal and colonic brush borders (BBs) contained both epithelial Na+/H+exchangers NHE2 and NHE3. We now show that, in the avian (chicken) colon, NHE2 is the major functional isoform under basal conditions and when stimulated by a low-NaCl diet. Hubbard chickens were maintained for 2 wk on a high- or low-NaCl diet. After the chickens were killed, the ileum and colon were removed, and BBs were prepared by Mg2+precipitation and22Na andd-[14C]glucose uptake determined in the BB vesicles. NHE2 and NHE3 were separated by differential sensitivity to HOE-694 (NHE2 defined as Na+/H+exchange inhibited by 50 μM HOE-694). Chickens on a low-Na+diet have increased plasma aldosterone (10 vs. 207 pg/ml). On the high-NaCl diet, both NHE2 and NHE3 contributed to ileal and colonic apical Na+/H+exchange, contributing equally in ileum, but NHE2 being the major component in colon (86%). Low-NaCl diet significantly increased ileal and colonic BB Na+/H+exchange; the increase in BB Na+/H+exchange in both ileum and colon was entirely due to an increase in NHE2 with no change in NHE3 activity. In contrast, low-NaCl diet decreased ileal and colonic Na+-dependentd-glucose uptake. Western analysis showed that low-Na+diet increased the amount of NHE2 in the ileal and colonic BB and decreased the amount of ileal Na+-dependent glucose transporter SGLT1. Both NHE2 and NHE3 were present in the apical but not basolateral membranes (BLM) of ileal and colonic epithelial cells. In summary, 1) NHE2 and NHE3 are both present in the BB and not BLM of chicken ileum and colon; 2) NHE2 is the major physiological colonic BB Na+/H+exchanger under basal conditions; 3) low-NaCl diet, which increases plasma aldosterone, increases ileal and colonic BB Na+/H+exchange and decreases Na+-dependentd-glucose uptake; 4) the stimulation of colonic BB Na+/H+exchange is due to increased activity and amount of NHE2; and 5) the inhibition of ileald-glucose uptake is associated with a decrease in SGLT1 amount. NHE2 is the major chicken colonic BB Na+/H+exchanger.
Hypotonic-stimulated taurine efflux in skate erythrocytes: regulation by tyrosine phosphatase activity
Authors: Musch Mark W. , Davis-Amaral Erin M. , Leibowitz Karen L. , Goldstein Leon
Published: December 2017

Treatment of skate erythrocytes with FCCP, dinitrophenol, or sodium azide lowers ATP levels and inhibits Na+-independent taurine uptake after hypotonic volume expansion. Inside-out vesicles isolated from hypotonic volume-expanded cells demonstrate greater Na+-independent taurine uptake, and pretreatment of cells with FCCP abolishes this stimulation. Addition of ATP to the vesicles does not restore stimulated taurine uptake, suggesting that ATP does not act as a ligand modulator on the transporter. Therefore the role of protein phosphorylation was investigated. Because known protein kinase inhibitors have previously been found to have little effect on taurine fluxes in skate erythrocytes, we focused on the effects of protein phosphatase inhibition. When volume-expanded cells were returned to isotonic medium, taurine flux returned to basal values more slowly after treatment with the tyrosine phosphatase inhibitor pervanadate, suggesting that dephosphorylation may regulate inactivation. A similar effect of phosphatase inhibitors was observed in the inside-out vesicles from volume-expanded cells: the reversal of stimulated taurine uptake takes place more slowly in vesicles prepared from cells that had been incubated with pervanadate. Band 3, a major protein involved in the taurine transport pathway, shows increased tyrosine phosphorylation after hypotonic volume expansion. Pervanadate treatment of the cells potentiates and prolongs the increased phosphorylation. Therefore tyrosine phosphorylation of band 3 may play an important role in the activation of taurine fluxes after volume expansion.
Peptidergic control of gastrointestinal blood flow in the estuarine crocodile,Crocodylus porosus
Authors: Kågström Jens , Olsson Catharina , Axelsson Michael , Franklin Craig E.
Published: December 2017

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.
β-Adrenergic modulation of triglyceridemia under increased energy expenditure
Authors: Mantha Line , Deshaies Yves
Published: December 2017

This study aimed to identify the metabolic steps involved in the acute hypotriglyceridemia brought about by increased energy expenditure (cold exposure) and to assess the causative involvement of some determinants of triglyceride (TG) metabolism as well as that of the β-adrenergic pathway. Rats were kept at 24°C or exposed to 10°C for 3 h after acute administration of the β-adrenergic antagonist propranolol (Prop) or vehicle. Cold exposure increased the rate of TG secretion (Triton WR1339 method) into the circulation by 50% ( P < 0.0005), an effect that was blunted by Prop. The cold-induced increase in TG secretion was closely related to changes in circulating nonesterified fatty acid levels, but not with serum insulin concentrations. Despite an increase in TG secretion, serum TG levels after acute cold exposure fell to 50% ( P < 0.002) of those measured at 24°C, indicating that the lowering of serum TG was entirely due to an increase in their rate of intravascular hydrolysis. This was confirmed by observing a 70% increase ( P < 0.002) in the rate of clearance of an exogenous TG emulsion in cold-exposed rats compared with those kept in the warm. Prop treatment before cold exposure decreased (∼30%, P < 0.005) the cold-induced stimulation of TG hydrolysis. The increased TG clearance rate in cold-exposed animals occurred in the absence of any change in the intravascular availability of lipoprotein lipase (LPL). In contrast, the activity of LPL displayed a tissue-specific response to cold exposure, being reduced by one-half in white adipose tissue ( P < 0.0005) and increased in brown adipose tissue (130%, P < 0.0001) and the heart (50%, P < 0.001). These findings show that, in the postprandial state, an acute increase in energy expenditure induced by cold exposure results in a lowering of serum TG entirely due to an increase in their rate of intravascular hydrolysis and that serum TGs are lowered despite an increase in the rate of TG secretion into the circulation. More efficient TG hydrolysis occurs independently of the intravascular availability of LPL. The study further shows that the effects of cold exposure on serum TG concentration and their rates of secretion and clearance are in large part mediated by the β-adrenergic pathway.
Anorectic effect of amylin is not transmitted by capsaicin-sensitive nerve fibers
Authors: Lutz Thomas A. , Althaus Janine , Rossi Rinaldo , Scharrer Erwin
Published: December 2017

Abdominal vagal and splanchnic afferents play an important role in the control of food intake in that they transmit various satiety signals to the central nervous system. Inasmuch as previous studies have shown that the anorectic effect of intraperitoneally injected amylin was not abolished by subdiaphragmatic vagotomy, the aim of the present study was to elucidate the role of splanchnic afferents in mediating amylin’s anorectic effect after intraperitoneal injection. Rats were pretreated intraperitoneally with the neurotoxin capsaicin, which destroys primary sensory (vagal and splanchnic) afferents. Sham-treated rats served as control. Capsaicin-pretreatment had no influence on the anorectic effects of amylin (5 μg/kg) and the related peptide, calcitonin gene-related peptide (CGRP; 5 μg/kg), in 24-h food-deprived rats. Abolition of cholecystokinin’s (3 μg/kg) anorectic effect agrees with previous studies and confirmed the effectiveness of the capsaicin pretreatment. In conclusion, the anorectic effects of intraperitoneally injected amylin and CGRP are not mediated by capsaicin-sensitive primary sensory neurons. Both anorectic peptides are, therefore, most likely to act within the central nervous system. Previous studies suggest that the relevant receptors might be located in neurons of the area postrema-nucleus of the solitary tract region.
Central action of adrenomedullin to prevent ethanolinduced gastric injury through vagal pathways in rats
Authors: Kaneko Hiroshi , Mitsuma Terunori , Nagai Hirofumi , Mori Shozaburo , Iyo Takashi , Kusugami Kazuo , Taché Yvette
Published: December 2017

Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP1 receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40–72% and rat α-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP1 receptor antagonist CGRP-(8—37) (9.6–19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal α-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or N G-nitro-l-arginine methyl ester (l-NAME) prevented AM protective action. l-Arginine but not d-arginine blockedl-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.
High-energy turnover at low temperatures: recovery from exhaustive exercise in Antarctic and temperate eelpouts
Authors: Hardewig I. , Van Dijk P. L. M. , Pörtner H. O.
Published: December 2017

Earlier work on Notothenioids led to the hypothesis that a reduced glycolytic capacity is a general adaptation to low temperatures in Antarctic fish. In our study this hypothesis was reinvestigated by comparing changes in the metabolic status of the white musculature in two related zoarcid species, the stenothermal Antarctic eelpout Pachycara brachycephalum and the eurythermal Zoarces viviparus during exercise and subsequent recovery at 0°C. In both species, strenuous exercise caused a similar increase in white muscle lactate, a drop in intracellular pH (pHi) by about 0.5 pH units, and a 90% depletion of phosphocreatine. This is the first study on Antarctic fish that shows an increase in white muscle lactate concentrations. Thus the hypothesis that a reduced importance of the glycolytic pathway is characteristic for cold-adapted polar fish cannot hold. The recovery process, especially the clearance of white muscle lactate, is significantly faster in the Antarctic than in temperate eelpout. Based on metabolite data, we calculated that during the first hour of recovery aerobic metabolism is increased 6.6-fold compared with resting rates in P. brachycephalum vs. an only 2.9-fold increase in Z. viviparus. This strong stimulation of aerobic metabolism despite low temperatures may be caused by a pronounced increase of free ADP levels, in the context of higher levels of pHiand ATP, which is observed in the Antarctic species. Although basal metabolic rates are identical in both species, the comparison of metabolic rates during situations of high-energy turnover reveals that the stenothermal P. brachycephalum shows a higher degree of metabolic cold compensation than the eurythermal Z. viviparus. Muscular fatigue after escape swimming may be caused by a drop of the free energy change of ATP hydrolysis, which is shown to fall below critical levels for cellular ATPases in exhausted animals of both species.
Effects of chronic inhibition of ACE and AT1receptors on glomerular injury in Dahl salt-sensitive rats
Authors: Otsuka Fumio , Yamauchi Takayoshi , Kataoka Hideo , Mimura Yukari , Ogura Toshio , Makino Hirofumi
Published: December 2017

To elucidate the contribution of the renin-angiontensin system (RAS) to glomerular injury in salt-sensitive hypertension, we investigated the chronic effects of the angiotensin I-converting enzyme inhibitor cilazapril and the angiotensin II type 1-receptor antagonist (AT1a) TCV-116 in Dahl-Iwai rats. Dahl salt-sensitive (S) rats receiving 8% salt diet for 6 wk were simultaneously treated with cilazapril ( n = 6), TCV-116 ( n = 6), or saline ( n = 14). The 8% salt diet markedly increased systolic blood pressure (SBP), urinary protein, and N-acetyl-β-glucosaminidase (NAG) excretion compared with 0.3% salt-treated S ( n = 6) or salt-resistant ( n = 6) rats. Although neither cilazapril nor TCV-116 reduced the elevated SBP, TCV-116 significantly lowered urinary protein and NAG excretion. Histologically, 8% salt treatment in S rats induced progressive sclerotic and proliferative glomerular changes, which were ameliorated by both drugs. TCV-116 increased the glomerular diameter. Immunofluorescence demonstrated the increased level of type III collagen in the mesangium of 8% salt-treated S rats, which was completely reversed by TCV-116. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that 8% salt treatment significantly increased the levels of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor B-chain and that TCV-116 significantly reduced the levels of PCNA and transforming growth factor-β1 (TGF-β1). Thus, although the chronic RAS-inhibition in salt-sensitive hypertension exerted a histologically renoprotective effect by both ways without lowering blood pressure, the RAS inhibition due to AT1ahad more beneficial advantages of reducing proteinuria and attenuating the levels of glomerular TGF-β1 and extracellular matrix.
Differential development of umbilical and systemic arteries. II. Contractile proteins
Authors: Arens Yvonne , Chapados Rene A. , Cox Blair E. , Kamm Kristine E. , Rosenfeld Charles R.
Published: December 2017

In fetal sheep, umbilical responsiveness to ANG II exceeds systemic vascular responsiveness. Fetal systemic vascular smooth muscle (VSM) exhibits an immature phenotype with decreased contractile protein contents, low 200-kDa myosin heavy chain (MHC) SM2, and significant nonmuscle MHC-B expression, whereas umbilical VSM phenotype is incompletely described. We tested the hypothesis that differences in vascular responsiveness could reflect dissimilarities in VSM phenotype. Actin, MHC, MHC isoforms, and active stresses were compared in strips of femoral arteries and aorta from near-term fetal ( n = 12) and adult ( n = 12) sheep to those in external and intra-abdominal umbilical arteries. Actin contents in fetal femoral artery and aorta were less ( P ≤ 0.006) than in external umbilical artery (7.37 ± 1.4 and 7.53 ± 0.7 vs. 21.6 ± 2.2 μg/mg wet wt, respectively) as were MHC contents (3.17 ± 0.4 and 2.84 ± 0.3 vs. 7.16 ± 0.7, respectively). Whereas 204- and 200-kDa MHC were expressed equally in fetal systemic arteries, umbilical and adult arteries predominantly expressed the 204-kDa isoform (SM1); only fetal systemic VSM expressed MHC-B. Fetal systemic artery stresses and myosin light chain phosphorylation were less than those in umbilical and adult arteries ( P < 0.001). Compared with umbilical and adult arteries, fetal systemic VSM is biochemically and functionally immature and thus umbilical VSM demonstrates precocious maturation resembling adult VSM in protein expression and function.
Monocarboxylate transporter MCT1 is located in the apical membrane and MCT3 in the basal membrane of rat RPE
Authors: Philp Nancy J. , Yoon Heeyong , Grollman Evelyn F.
Published: December 2017

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier and regulates the movement of nutrients, water, and ions between the choroidal blood supply and the retina. The transport properties of the RPE maintain retinal adhesion and regulate the pH and osmolarity in the space surrounding the photoreceptor cell outer segments. In this report we identify two monocarboxylate transporters, MCT1 and MCT3, expressed in rat RPE. On the basis of Northern and Western blot analyses, MCT1 is expressed in both the neural retina and the RPE, whereas the expression of MCT3 is restricted to the RPE. Using indirect immunolocalization we show that the two transporters are polarized to distinct membrane domains. MCT1 antibody labels the apical surface and the apical processes of the RPE. A polyclonal antibody produced against the carboxy terminus of rat MCT3 labels only the basolateral membrane of the RPE. The demonstration of MCT1 on the apical membrane and MCT3 on the basal membrane identifies specific proteins involved in the discriminate and critical regulation of water and lactate transport from the retina to the choroid.