bluuebunny/crossref_metadata_2025 huggingface dataset:
Metallothionein response in gills ofOreochromis mossambicusexposed to copper in fresh water
Authors: Dang Zhichao , Lock Robert A. C. , Flik Gert , Bonga Sjoerd E. Wendelaar
Published: December 2017

Freshwater Oreochromis mossambicus (tilapia) were exposed to 3.2 μmol/l Cu(NO3)2in the water for up to 80 days, and copper (Cu) and immunoreactive metallothionein (irMT) were localized in the branchial epithelium. Cu was demonstrated in mucous cells (MC), chloride cells (CC), pavement cells (PC), respiratory cells (RC), and basal layer cells (BLC) via autometallography combined with alcian blue staining for MC and Na+-K+-ATPase immunostaining for CC and, on the basis of their location in the epithelium of PC, RC, and BLC. In control fish (water with Cu concentration ≤90 nmol/l) incidentally irMT was observed in the area where progenitor cells of the branchial epithelia reside, as demonstrated by proliferating cell nuclear antigen staining. This was also the area where the first increase irMT expression of the Cu exposure was observed. After 2 days of exposure to Cu, irMT was found in CC and PC. From 5 days on, a pronounced irMT staining was observed in BLC of branchial epithelium, which then appeared to migrate and differentiate into mature CC, PC, and RC. We conclude that MT expression in mature CC, PC, and RC requires exposure to Cu in a earlier stage of development of these cells. Once expression is initiated in undifferentiated cells, MT remains expressed throughout the life cycle of the cell.
Altered daily rhythms of brain and pituitary indolamines and neuropeptides in long-term hypoxic rats
Authors: Poncet Ludovic , Pequignot Jean-Marc , Cottet-Emard Jean-Marie , Dalmaz Yvette , Denoroy Luc
Published: December 2017

To determine whether sustained hypoxia alters daily rhythms in brain and pituitary neurotransmitters, the daily variations in vasoactive intestinal peptide-like immunoreactivity (VIP-LI), neuropeptide Y-like immunoreactivity (NPY-LI), serotonin (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) content were determined in discrete brain regions, pineal gland and anterior pituitary of hypoxic (10% O2; 14 days) and normoxic rats. Hypoxia suppressed daily variations in VIP-LI in the suprachiasmatic nuclei (SCN) and the anterior pituitary, enhanced the daily rhythmicity in serotonergic elements of the caudal part of the dorsomedial medulla oblongata (DMMc), and even induced daily variations in NPY-LI in the DMMc as well as in the ventrolateral medulla oblongata. In addition, punctual alterations in the rhythmicity of 5-HT and 5-HIAA in the pineal gland and of plasma corticosterone were observed in hypoxic rats. Thus results of this study indicate that a permanent nonphotic stimulus, such as sustained hypoxia, may affect the functioning of the internal clock located in the SCN and may alter the daily rhythmicity in neurotransmitter content of some brain nuclei and the pituitary gland.
Cardiovascular and neuroendocrine responses to exercise in hypoxia during impaired neural feedback from muscle
Authors: Kjær Michael , Hanel Birgitte , Worm Lars , Perko Grazyna , Lewis Steven F. , Sahlin Kent , Galbo Henrik , Secher Niels H.
Published: December 2017

Reflex mechanisms from contracting skeletal muscle have been shown to be important for cardiovascular, neuroendocrine, and extramuscular fuel-mobilization responses in exercise. Furthermore, because hypoxia results in exaggerated metabolic changes in contracting muscle, the present study evaluated whether enhancement of cardiovascular and neuroendocrine responses by hypoxia during exercise is influenced by neural feedback from contracting muscle. Seven healthy males cycled at 46% maximal O2uptake for 20 min both during normoxia and at 11.5% O2, and both without and with epidural anesthesia (EA; 20 ml 0.25% bupivacain, resulting in cutaneous hypesthesia below T10-T12 and 25% reduction in maximal leg strength). Exercise to exhaustion was also performed at 7.8% O2. The exercise-induced increases in heart rate; cardiac output; leg blood flow; plasma concentrations of growth hormone, adrenocorticotropin, cortisol, and catecholamines; renin activity; glucose production and disappearance; norepinephrine spillover [2,190 ± 341 ng/min (exercise at 11.5% O2) vs. 988 ± 95 ng/min (exercise during normoxia)]; lactate release from and glucose uptake in the leg; and the decreases in plasma insulin and free fatty acids were exaggerated in hypoxia ( P < 0.05). In muscle, concentrations of lactate, creatine, and inosine 5′-monophosphate were higher, and those of phosphocreatine were lower after exercise in hypoxia compared with normoxia. The exercise-induced increase in mean arterial blood pressure was not affected by hypoxia, but it was reduced by EA [108 ± 4 mmHg (control) vs. 97 ± 4 mmHg (EA); P < 0.05], and the reduction was more pronounced during severe hypoxia compared with normoxia. Apart from this, time to exhaustion at extreme hypoxia, circulatory responses, concentrations of neuroendocrine hormones, and extramuscular substrate mobilization were not diminished by EA. In conclusion, in essence the hypoxia-induced enhancement of systemic adaptation to exercise is not mediated by neural feedback from working muscle in humans.
In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response
Authors: Memon Riaz A. , Fuller John , Moser Arthur H. , Feingold Kenneth R. , Grunfeld Carl
Published: December 2017

Plasma platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes PAF and oxidized phospholipids and is associated with lipoproteins in the circulation. Endotoxin [lipopolysaccharide (LPS)], a potent inducer of the acute phase response (APR), produces marked changes in several proteins that play important roles in lipoprotein metabolism. We now demonstrate that LPS produces a 2.5- to 3-fold increase in plasma PAF-AH activity in Syrian hamsters. The plasma PAF-AH activity is found in the high-density lipoprotein (HDL) fraction and is increased threefold with LPS treatment despite a decrease in plasma HDL levels, indicating that plasma PAF-AH activity is increased per HDL particle. LPS markedly increased PAF-AH mRNA levels in liver, spleen, lung, and small intestine. The maximal increase in plasma PAF-AH activity and mRNA expression in liver and spleen is seen 24 h after LPS treatment. Both tumor necrosis factor and interleukin-1 modestly increased plasma PAF-AH activity and mRNA levels in liver and spleen, suggesting that they may partly mediate the effect of LPS on PAF-AH. Surgical removal of spleen had no effect on basal or LPS-induced plasma PAF-AH activity, suggesting that spleen per se may not contribute to plasma PAF-AH activity. Finally, LPS, turpentine and zymosan increased plasma PAF-AH activity in mice and/or rats, indicating that multiple APR inducers upregulate plasma PAF-AH and this effect is consistent across different rodent species. Taken together, our results indicate that plasma PAF-AH activity and mRNA expression is markedly upregulated during the host response to infection and inflammation. An increase in plasma PAF-AH may enhance the degradation of PAF as well as alter the structure and function of HDL during infection and inflammation.
Thermoregulatory responses of the inbred heat-tolerant FOK rat to cold
Authors: Yahata Takehiro , Furuyama Fujiya , Nagashima Tomoaki , Moriya Mitsuru , Kikuchi-Utsumi Kazue , Kawada Teruo , Kuroshima Akihiro
Published: December 2017

The responses of inbred heat-tolerant FOK rats to cold were compared with those of Wistar King A/H (WKAH) and Std:Wistar (WSTR) strains. The fall of colonic temperature during cold exposure was unexpectedly smaller in FOK than in other groups, but the onset of shivering was delayed in FOK. Norepinephrine (NE)-induced in vivo oxygen consumption and the mitochondrial uncoupling protein 1 level of brown adipose tissue (BAT) were not different among the groups, but the cold-induced increases in in vivo oxygen consumption as well as plasma glycerol and free fatty acids were higher in FOK than in other groups. In vitro NE-induced oxygen consumption of BAT was less in FOK than WSTR, but not WKAH. The magnitude of the NE-induced increase in blood flow through BAT was higher in FOK than in other groups. These results suggest that FOK paradoxically have a high capacity for nonshivering thermogenesis in spite of their high capacity for heat tolerance, probably due to an increased lipid utilization and improved circulation of BAT.
Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract
Authors: Duan Yu-Fei , Kopin Irwin J. , Goldstein David S.
Published: December 2017

The present study assessed whether the baroreflex inhibition elicited by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) involves altered activity in the nucleus of the solitary tract (NTS). Unit recordings were made from 107 neurons in the NTS in anesthetized rabbits. Intravenous phenylephrine was used to induce a pressor response and to activate baroreflexes. Of the neurons that responded to pressor responses, two-thirds were excited and one-third was inhibited. Stimulation of the PVN inhibited 70% of the phenylephrine-responsive NTS neurons, with or without concurrent baroreceptor stimulation. When PVN stimulation was delivered concurrently with phenylephrine injection, more NTS neuronal inhibition and less excitation occurred than with phenylephrine alone. Usually PVN stimulation inhibited NTS neurons that were excited by pressor responses; less commonly, PVN stimulation excited NTS neurons that were inhibited by pressor responses. The findings are consistent with the view that PVN activation during the defense reaction inhibits baroreflexes by altering firing of NTS neurons.
Sympathetic outflow to muscle in humans during short periods of microgravity produced by parabolic flight
Authors: Iwase Satoshi , Mano Tadaaki , Cui Jian , Kitazawa Hiroki , Kamiya Atsunori , Miyazaki Seiji , Sugiyama Yoshiki , Mukai Chiaki , Nagaoka Shunji
Published: December 2017

We have investigated the changes in muscle sympathetic nerve activity (MSNA) from the tibial nerve during brief periods of microgravity (μG) for ∼20 s produced by parabolic flight. MSNA was recorded microneurographically from 13 quietly seated human subjects with their knee joints extended in a jet aircraft simultaneously with the electrocardiogram, the blood pressure wave (measured with a Finapres), the respiration curve, and the thoracic fluid volume (measured by impedance plethysmography). During quiet and seated parabolic flight, MSNA was activated in hypergravity and was suppressed in μG phasically. At the entry to hypergravity at 2 G just before μG, the thoracic fluid volume was reduced by 3.2 ± 3%, and the arterial blood pressure was lowered transiently and then gradually elevated from 89.5 ± 1.7 to 100.2 ± 1.7 mmHg, which caused the enhancement of MSNA by 91.4 ± 14.2%. At the entry to μG, the thoracic fluid volume was increased by 3.4%, which lowered the mean blood pressure to 77.9 ± 2.3 mmHg and suppressed the MSNA by 17.2%. However, this suppression lasted only ∼10 s, followed by an enhancement of MSNA that continued for several seconds. We conclude that MSNA is suppressed and then enhanced during μG produced by parabolic flight. These changes in MSNA are in response not only to intrathoracic fluid volume changes but also to arterial blood pressure changes, both of which are caused by body fluid shifts induced by parabolic flight, and these changes are quite phasic and transient.
Activity and expression of the 20S proteasome are increased in skeletal muscle during sepsis
Authors: Hobler Scott C. , Williams Arthur , Fischer David , Wang Jing Jing , Sun Xiaoyan , Fischer Josef E. , Monaco John J. , Hasselgren Per-Olof
Published: December 2017

Recent studies suggest that sepsis stimulates ubiquitin-dependent protein breakdown in skeletal muscle. In this proteolytic pathway, ubiquitinated proteins are recognized, unfolded, and degraded by the multicatalytic 26S protease complex. The 20S proteasome is the catalytic core of the 26S protease complex. The role of the 20S proteasome in the regulation of sepsis-induced muscle proteolysis is not known. We tested the hypothesis that sepsis increases 20S proteasome activity and the expression of mRNA for various subunits of this complex. Proteolytic activity of isolated 20S proteasomes, assessed as activity against fluorogenic peptide substrates, was increased in extensor digitorum longus muscles from septic rats. The proteolytic activity was inhibited by specific proteasome blockers. Northern blot analysis revealed an approximately twofold increase in the relative abundance of mRNA for the 20S α-subunits RC3 and RC9 and the β-subunit RC7. However, Western blot analysis did not show any difference in RC9 protein content between sham-operated and septic rats. The increased activity and expression of the 20S proteasome in muscles from septic rats lend further support for a role of the ubiquitin-proteasome-pathway in the regulation of sepsis-induced muscle proteolysis.
A five-parameter logistic equation for investigating asymmetry of curvature in baroreflex studies
Authors: Ricketts James H. , Head Geoffrey A.
Published: December 2017

Baroreceptor reflex curves are usually analyzed using a symmetric four-parameter function. We wished to ascertain the validity of assuming symmetry in the baroreflex curve and also of constraining the curves to pass through the resting blood pressure and heart rate (HR) values. Therefore, we have investigated the suitability of a new five-parameter asymmetric logistic model for analysis of baroreflex curves from rabbits and dogs. The five-parameter model is an extension of the usual four-parameter model and reduces to that model when the fitted data are symmetrical. Using 30 data sets of blood pressure versus renal sympathetic nerve activity (RSNA) and HR from six conscious rabbits, we compared the five-parameter curves with the four-parameter model. We also tested the effect of forcing these baroreflex curves through the resting point. We found that the five-parameter model reduced the unexplained variation and gave small but important improvements to the estimates of plateaus for RSNA and HR and the HR gain. Although forcing the HR curves through the resting values had little effect, this procedure, when applied to RSNA, produced a worse curve fit by increasing the unexplained variation with alteration to most of the estimated curve parameters. The mean arterial pressure-HR baroreflex relationship from six conscious dogs was also analyzed and showed clear evidence of systematic asymmetry. We conclude that the asymmetric model is a valuable extension to the symmetric logistic model when examining baroreceptor reflexes, giving improved estimates of the parameters and a new approach to examining the mechanisms contributing to baroreflex curve asymmetry. Furthermore, forcing the curves through the resting value is a statistically questionable practice when analyzing RSNA, because it affects the parameter estimates.
Basic FGF decreases clearance receptor of natriuretic peptides in fetoplacental artery endothelium
Authors: Itoh Hiroaki , Zheng Jing , Bird Ian M. , Nakao Kazuwa , Magness Ronald R.
Published: December 2017

Atrial natriuretic peptide (ANP) is present in the fetoplacental circulation of humans and sheep. The ANP-A receptor is the specific membrane receptor for ANP, which produces cGMP. The clearance receptor of natriuretic peptide (CR) is postulated to modulate local concentrations of ANP, thereby modulating cGMP production through the ANP-A receptor. Recently we reported that fetoplacental basic fibroblast growth factor (bFGF) and cGMP levels are increased dramatically during the third trimester of ovine gestation. Therefore we hypothesized that bFGF will downregulate CR expression in cultured ovine fetoplacental artery endothelial (OFPAE) cells via the mitogen-activated protein kinase (MAPK) signal cascade mechanism, thereby causing augmentation of ANP-mediated cGMP production. Western analysis and/or RT-PCR of CR expression were performed after treatment of OFPAE cells with bFGF (10 pg/ml–1 μg/ml) with or without 50 μM PD-98059, a selective inhibitor of MAPK kinase. To investigate the possible effects of CR downregulation on the functional modulation of ANP-A receptor activation, cGMP production (20 min) by OFPAE cells was measured in response to ANP (10 pM–1 μM) with or without pretreatment (24 h) of 10 ng/ml bFGF. CR expression in OFPAE cells was dose dependently downregulated by 1–10 ng/ml bFGF treatment (maximum −69%), which was completely reversed by pretreatment with PD-98059. Treatment of OFPAE cells with 10 ng/ml bFGF (24 h) did not alter maximum ANP-A activity (cGMP production/20 min), but decreased the apparent ED50of ANP to stimulate cGMP production from 2.5 to 0.83 nM, suggesting the possibility that bFGF-mediated downregulation of CR may elevate ANP-mediated cGMP production responses. Thus bFGF downregulates CR mRNA and protein expressions via the MAPK cascade in OFPAE cells.
Increase in intake with sham feeding experience is concentration dependent
Authors: Davis John D. , Smith Gerard P. , Singh Bramdeo , McCann Daniel P.
Published: December 2017

Most sham feeding studies show that about three sham feeding tests are required for intake to reach maximum. One study, however, using a dilute solution, reported maximum sham intake in the first sham feeding test, suggesting that the progressive rise in sham intake may be concentration dependent. We tested this hypothesis with six groups of rats given five sham feeding tests each with one of six concentrations of sweetened condensed milk (0.5:1, 1:1, 2:1, 4:1, 8:1, 16:1, water-to-milk dilutions). It took three sham tests for intake to reach maximum with the three most concentrated solutions, but only one with the three weakest. Thus the intake of concentrated solutions of milk is limited by two negative feedback signals, one derived from the accumulation of fluid in the gastrointestinal tract, the other from a labile signal that loses its effectiveness with sham feeding experience. In contrast, the intake of weak concentrations is limited only by the nonlabile negative feedback signal because the labile signal is missing.
Interoceptive stress activates glucagon-like peptide-1 neurons that project to the hypothalamus
Authors: Rinaman Linda
Published: December 2017

This study tested the hypothesis that systemic stressors in rats activate glucagon-like peptide-1 (GLP-1)-immunoreactive neurons in the caudal brain stem, including those that project to the paraventricular nucleus of the hypothalamus (PVN). Neural tracer was microinjected into the PVN to retrogradely label brain stem neurons. Seven to ten days later, rats were injected with lithium chloride (LiCl; 50 mg/kg). Additional non-tracer-injected rats were treated with lipopolysaccharide (LPS; 100 μg/kg) or CCK (100 μg/kg) or were allowed to consume a very large meal. Rats were killed 90–120 min after drug treatment or 30 min after the meal. Brains were processed for immunocytochemical localization of c-Fos (a marker of neuronal activation), GLP-1, and, when appropriate, neural tracer. The majority of GLP-1 neurons were activated to express c-Fos after LiCl, LPS, or CCK treatment, including (in LiCl-treated rats) those projecting to the PVN. In contrast, GLP-1 neurons rarely expressed c-Fos after ingestion of a large meal, despite prominent activation of other brain stem neurons. These results suggest that GLP-1 neurons are uniquely activated in situations of interoceptive stress, and may participate in adaptive hypothalamic stress responses.
EEG and ocular correlates of circadian melatonin phase and human performance decrements during sleep loss
Authors: Cajochen Christian , Khalsa Sat Bir S. , Wyatt James K. , Czeisler Charles A. , Dijk Derk-Jan
Published: December 2017

The aim of this study was to quantify the associations between slow eye movements (SEMs), eye blink rate, waking electroencephalogram (EEG) power density, neurobehavioral performance, and the circadian rhythm of plasma melatonin in a cohort of 10 healthy men during up to 32 h of sustained wakefulness. The time course of neurobehavioral performance was characterized by fairly stable levels throughout the first 16 h of wakefulness followed by deterioration during the phase of melatonin secretion. This deterioration was closely associated with an increase in SEMs. Frontal low-frequency EEG activity (1–7 Hz) exhibited a prominent increase with time awake and little circadian modulation. EEG alpha activity exhibited circadian modulation. The dynamics of SEMs and EEG activity were phase locked to changes in neurobehavioral performance and lagged the plasma melatonin rhythm. The data indicate that frontal areas of the brain are more susceptible to sleep loss than occipital areas. Frontal EEG activity and ocular parameters may be used to monitor and predict changes in neurobehavioral performance associated with sleep loss and circadian misalignment.
Sympathetic control of BP and BP variability in borderline hypertensive rats on high- vs. low-salt diet
Authors: Brown David R. , Li Sheng-Gang , Lawler James E. , Randall David C.
Published: December 2017

This experiment tested the effect of a high-salt diet on the interaction between arterial blood pressure (BP) and sympathetic nerve activity (SNA) at rest and during a controlled behavioral stress at an early stage in the development of hypertension in borderline hypertensive rats (BHR). Ten rats were maintained on a high-salt diet (8% NaCl) while 14 were fed a low-salt diet (0.8% NaCl) for 8 wk. They were trained in a Pavlovian paradigm by following a conditional stimulus tone (CS+) with a 0.5-s shock. SNA and BP were measured by implanted electrodes around the left renal nerve and a catheter in the femoral artery, respectively. There were no detectable between-group differences in BP or in BP variability in the resting animal at the end of the 8-wk dietary treatment. Moreover, there were no significant between-group differences in the changes in SNA evoked by the CS+ tone. Conversely, the amplitude of the initial conditional increase in BP was significantly ( P< 0.05) larger in the high-salt (6 ± 0.6 mmHg; mean ± SEM) compared with the low-salt (4 ± 0.4 mmHg) group. In addition, the BP excursion (peak/trough) during CS+ was larger in the high (18.2 ± 6.1 mmHg)- vs. low-salt (5.8 ± 0.4 mmHg) diet-fed subjects. The ratio of the average percent change in mean BP to the average percent change in SNA at the beginning of CS+ was 0.029 ± 0.004 for the low-salt group and 0.041 ± 0.006 for the high-salt group. We find that, before the development of overt hypertension, the enhanced conditional BP response in the high-salt BHR appears to reside at the interface between changes in SNA and the effector response and not within the central nervous system. These observations help explain the increasing BP variability typically observed with the development of hypertension in humans.
Increase of total creatine in human brain after oral supplementation of creatine-monohydrate
Authors: Dechent P. , Pouwels P. J. W. , Wilken B. , Hanefeld F. , Frahm J.
Published: December 2017

The effect of oral creatine supplementation on brain metabolite concentrations was investigated in gray matter, white matter, cerebellum, and thalamus of healthy young volunteers by means of quantitative localized proton magnetic resonance spectroscopy in vivo (2.0 T, stimulated echo acquisition mode sequence; repetition time = 6,000 ms, echo time = 20 ms, middle interval = 10 ms, automated spectral evaluation). Oral consumption of 4 × 5 g creatine-monohydrate/day for 4 wk yielded a statistically significant increase (8.7% corresponding to 0.6 mM, P < 0.001) of the mean concentration of total creatine (tCr) when averaged across brain regions and subjects ( n = 6). The data revealed considerable intersubject variability (3.5–13.3%), with the smallest increases observed for the two male volunteers with the largest body weights. A regional analysis resulted in significant increases of tCr in gray matter (4.7%), white matter (11.5%), and cerebellum (5.4%) and was most pronounced in thalamus (14.6% corresponding to 1.0 mM). Other findings were significant decreases of N-acetyl-containing compounds in cerebellum and thalamus as well as of choline-containing compounds in thalamus. All cerebral metabolic alterations caused by oral Cr were reversible, as evidenced by control measurements at least 3 mo after the diet. This work demonstrates that excess consumption of Cr yields regionally dependent increases of the tCr concentration in human brain over periods of several weeks.
Patterning of somatosympathetic reflexes
Authors: Kerman I. A. , Yates B. J.
Published: December 2017

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (∼60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (∼20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.
Cloning of mouse prostaglandin transporter PGT cDNA: species-specific substrate affinities
Authors: Pucci Michael L. , Bao Yi , Chan Brenda , Itoh Shigekazu , Lu Run , Copeland Neal G. , Gilbert Debra J. , Jenkins Nancy A. , Schuster Victor L.
Published: December 2017

We recently identified and/or cloned the PG transporter PGT in the rat (rPGT) (Kanai, N., R. Lu, J. A. Satriano, Y. Bao, A. W. Wolkoff, and V. L. Schuster, Science 268: 866–869, 1995) and the human (hPGT) (Lu, R., and V. L. Schuster, J. Clin. Invest. 98: 1142–1149, 1996). Here we have cloned and expressed the mouse PGT (mPGT) cDNA. The tissue distribution of mPGT mRNA expression is significantly more restricted than that of rPGT and hPGT mRNA. Although the deduced amino acid sequence of mPGT is similar to the rat (91% identity) and human (82% identity) homologues, it has three regions of dissimilarity: amino acids 128–163 and 283–298, and valine 610 and isoleucine 611 (predicted to lie within putative transmembrane span 12). Affinities of hPGT, rPGT, and mPGT for several PG substrates differed, with hPGT having the highest [low Michaelis constant ( Km)] and mPGT the lowest affinity. A chimeric protein, linking the N-terminal domain of mPGT with the C-terminal domain of hPGT, had affinity for PGE2indistinguishable from that of hPGT, indicating that the C-terminal domain dictates Km. We mutagenized mouse valine 610 and isoleucine 611 to their corresponding human residues (methionine and glycine, respectively); however, these changes did not convert the inhibition constant of mPGT to that of hPGT. The mouse gene was localized to chromosome 9 in a region syntenic with the region of human chromosome 3 containing the hPGT gene. These studies highlight the species-dependence of tissue expression and function of PGT and lay the groundwork for the use of the mouse as a model system for the study of PGT function.
Potentiation of carbachol-induced amylase release by propionate in guinea pig and vole pancreatic acini
Authors: Harada Etsumori , Mitani Megumi , Takeuchi Takashi
Published: December 2017

The action of propionate, one of the major end products of microbial fermentation in herbivores was investigated in isolated, perifused pancreatic acini of guinea pigs, voles, and mice. With the use of guinea pig acini, 100 μM propionate had no effect, whereas 300 and 600 μM increased amylase release by six- and ninefold, respectively. Simultaneous perifusion of carbachol (CCh) 10 μM plus propionate 100 μM in guinea pig acini produced a potentiated secretory response that was 130% higher than the summated value obtained with CCh and propionate alone. The potentiation by propionate (100 μM) of CCh (10 μM)-induced amylase release was also obtained in vole pancreatic acini, but the mouse pancreatic preparation did not exhibit a similar potentiation. In contrast to CCh, propionate (100–600 μM) alone had no significant effect on intracellular Ca2+concentration ([Ca2+]i) and did not alter [Ca2+]ielicited by CCh. Ca ionophore A23187 (5 μM)-induced amylase release in guinea pig acini was enhanced twofold by the addition of propionate. Cellular cAMP content was increased slightly by propionate, but did not alter dose dependently. The cAMP level with combinations of CCh and propionate was almost same as that with CCh alone and propionate alone. Staurosporine did not modify amylase secretion induced by a combination of CCh and propionate. These results suggest that propionate, in addition to a direct action on amylase release, potentiates CCh-induced amylase release in guinea pig and vole acini via a secretory pathway not associated with an increase in [Ca2+]iand cellular cAMP.
Mecamylamine blocks the [Asp1,Val5]-ANG II-induced attenuation of salt gland activity in Pekin ducks
Authors: Butler David Gordon
Published: December 2017

An intravenous injection of 2 μg of [Asp1,Val5]-ANG II attenuated fluid secretion by the nasal salt glands of Pekin ducks. Ganglionic blockade with mecamylamine stopped salt gland secretion. Flow was reestablished by intravenous methacholine bromide during ganglionic blockade. A second injection of 2 μg of [Asp1,Val5]-ANG II failed to attenuate secretion during ganglionic blockade, showing that the peptide acts via the central nervous system and postganglionic parasympathetic nerves that supply the salt glands. Sympathetic nerves are located in the walls of blood vessels within the salt glands, and adrenergic fibers with “varicosities” supply extensively the secretory tubules. [Asp1,Val5]-ANG II decreased salt gland secretion both before and after α1-adrenergic blockade with prazosin, showing that the lowered activity was not caused by the release of norepinephrine from nerve endings and/or duck adrenal chromaffin cells. β-Adrenergic blockade with propranolol also failed to prevent the attenuation of secretion in response to an intravenous injection of 2 μg of [Asp1,Val5]-ANG II, which showed that epinephrine did not mediate the response to the peptide.
Superoxide dismutase gene expression in skeletal muscle: fiber-specific adaptation to endurance training
Authors: Hollander J. , Fiebig R. , Gore M. , Bejma J. , Ookawara T. , Ohno H. , Ji L. L.
Published: December 2017

The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity ( P < 0.01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% ( P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities ( P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.
Direct evidence of acute stress-induced facilitation of ACTH response to subsequent stress in rats
Authors: Andrés Rosa , Martí Octavi , Armario Antonio
Published: December 2017

To determine the role of glucocorticoids in the appearance of the facilitatory effect of stress on the ACTH response to a subsequent stress, sham-operated (Sham) rats and rats adrenalectomized (ADX) and supplemented with 50 mg/l corticosterone (B) in the drinking saline (ADX + B) were subjected to 1 min of immobilization stress (Imo) four consecutive times with an interstressor interval of 90 min. Sham rats showed a similar pattern of ACTH response to the first and fourth exposures to Imo. ADX + B rats showed an exacerbated ACTH response to the fourth Imo, despite higher prestress levels than those observed before the first Imo. In another experiment, no facilitatory effect of previous stress on ACTH response was found in ADX rats, but supplementation with B in the drinking saline for 1 wk resulted in facilitation of the ACTH response. We conclude that repeated exposure to a short-time stress induces a facilitatory effect on the ACTH response that is uncovered by eliminating stress-induced glucocorticoid release but needs B doses resulting in approximately basal circulating glucocorticoid levels to be induced or expressed.
Cats increase fatty acid oxidation when isocalorically fed meat-based diets with increasing fat content
Authors: Lester Tammy , Czarnecki-Maulden Gail , Lewis Douglas
Published: December 2017

This study tested the hypothesis that sedentary cats have the ability to adapt to high-fat carnivore diets by increasing fat oxidation. Twenty-four hour indirect calorimetry was used to determine total energy expenditure (TEE) and macronutrient oxidation in six vasectomized male (VAS) and six ovariectomized female (OVX) cats isocalorically fed lower-fat (53% fat, 45% protein) and higher-fat (71% fat, 26% protein) meat-based diets at maintenance for 8 days. Fat oxidation increased linearly with fat intake with a mean slope of 0.91 g fat oxidized/g fat intake ( P < 0.001), with no change in TEE. However, VAS male cats were able to more precisely match fat oxidation with fat intake than OVX female cats ( P < 0.02). Body fat content did not significantly influence fat oxidation. These results demonstrate that cats maintain body weight during short-term isocaloric feeding of a high-fat carnivore-type diet in part by increasing fat oxidation commensurate with increases in fat intake. This ability may be an important mechanism underlying the resistance of cats to obesity, despite habitual consumption of high-fat diets.
Effect of adrenocorticotrophic hormone on sodium appetite in mice
Authors: Denton D. A. , Blair-West J. R. , McBurnie M. I. , Miller J. A. P. , Weisinger R. S. , Williams R. M.
Published: December 2017

A main vector of the effects of stress is secretion of corticotrophin releasing factor (CRF), adrenocorticotrophin (ACTH), and adrenal steroids. Systemic administration of ACTH (2.8 μg/day sc) for 7 days in BALB/c mice caused a very large increase of voluntary intake of 0.3 M NaCl equivalent to turnover of total body sodium content each day. Intracerebroventricular infusion of ACTH (20 ng/day) had no effect. Intracerebroventricular infusion of ovine CRF (10 ng/h for 7 days) caused an increase of sodium intake. The large sodium appetite-stimulating effect of systemic ACTH was not influenced by concurrent systemic infusion of captopril (2 mg/day). Induction of stress by immobilization of mice on a running wheel caused an increase in Na appetite associated with a 50% decrease of thymus weight, indicative of corticosteroid effects. The present data suggest that stress and the hormone cascade initiated by stress evoke a large sodium appetite in mice, which may be an important survival mechanism in environmental conditions causing stress.
Effect of an exercise-heat acclimation program on body fluid regulatory responses to dehydration in older men
Authors: Takamata Akira , Ito Tomoyuki , Yaegashi Kazuhiro , Takamiya Hisatake , Maegawa Yasuyo , Itoh Toshiyuki , Greenleaf John E. , Morimoto Taketoshi
Published: December 2017

We examined if an exercise-heat acclimation program improves body fluid regulatory function in older subjects, as has been reported in younger subjects. Nine older (Old; 70 ± 3 yr) and six younger (Young; 25 ± 3 yr) male subjects participated in the study. Body fluid regulatory responses to an acute thermal dehydration challenge were examined before and after the 6-day acclimation session. Acute dehydration was produced by intermittent light exercise [4 bouts of 20-min exercise at 40% peak rate of oxygen consumption (V˙o 2 peak) separated by 10 min rest] in the heat (36°C; 40% relative humidity) followed by 30 min of recovery without fluid intake at 25°C. During the 2-h rehydration period the subjects drank a carbohydrate-electrolyte solution ad libitum. In the preacclimation test, the Old lost ∼0.8 kg during dehydration and recovered 31 ± 4% of that loss during rehydration, whereas the Young lost ∼1.2 kg and recovered 56 ± 8% ( P < 0.05, Young vs. Old). During the 6-day heat acclimation period all subjects performed the same exercise-heat exposure as in the dehydration period. Exercise-heat acclimation increased plasma volume by ∼5% ( P < 0.05) in Young subjects but not in Old. The body fluid loss during dehydration in the postacclimation test was similar to that in the preacclimation in Young and Old. The fractional recovery of lost fluid volume during rehydration increased in Young (by 80 ± 9%; P < 0.05) but not in Old (by only 34 ± 5%; NS). The improved recovery from dehydration in Young was mainly due to increased fluid intake with a small increase in the fluid retention fraction. The greater involuntary dehydration (greater fluid deficit) in Old was accompanied by reduced plasma vasopressin and aldosterone concentrations, renin activity, and subjective thirst rating ( P < 0.05, Young vs. Old). Thus older people have reduced ability to facilitate body fluid regulatory function by exercise-heat acclimation, which might be involved in attenuation of the acclimation-induced increase in body fluid volume.
Role of ETB receptors and nitric oxide in adrenal catecholamine secretion in anesthetized dogs
Authors: Hosokawa Akio , Nagayama Takahiro , Masada Kimiya , Yoshida Makoto , Suzuki-Kusaba Mizue , Hisa Hiroaki , Kimura Tomohiko , Satoh Susumu
Published: December 2017

We examined the effects of sarafotoxin 6c (S6c), an endothelin-B (ETB) receptor agonist, on adrenal catecholamine secretion in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered intra-arterially into the adrenal gland through the phrenicoabdominal artery. Infusion of S6c attenuated increases in adrenal catecholamine output induced by splanchnic nerve stimulation. The inhibitory effect of S6c on the catecholamine secretion response was suppressed with a selective ETB receptor antagonist N- cis2,6-dimethylpiperidinocarbonyl-l-γ-methylleucyl-d-1-methoxycarbonyltryptophanyl-d-norleucine (BQ-788), a nitric oxide synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester, and a neuronal NOS inhibitor 7-nitroindazole monosodium salt (7-NINA). Similar results were obtained with the catecholamine secretion response induced by injection of ACh. 7-NINA alone did not affect these catecholamine secretion responses. These results suggest that ETB receptors play an inhibitory role in adrenal catecholamine secretion by activating neuronal NOS, whereas neuronal NOS is unlikely to be involved in regulation of adrenal catecholamine secretion in the absence of simultaneous ETB receptor stimulation.
Lesions of the C1 catecholaminergic neurons of the ventrolateral medulla in rats using anti-DβH-saporin
Authors: Madden Christopher J. , Ito Satoru , Rinaman Linda , Wiley Ronald G. , Sved Alan F.
Published: December 2017

Phenylethanolamine- N-methyltransferase (PNMT)-containing neurons in the rostral ventrolateral medulla (RVLM) are believed to play a role in cardiovascular regulation. To determine whether injection of anti-dopamine β-hydroxylase (DβH)-saporin directly into the RVLM in rats could selectively destroy these cells and thereby provide an approach for evaluating their role in cardiovascular regulation, we studied rats 2 wk after unilateral injection of 21 ng anti-DβH-saporin into the RVLM. There was an ∼90% reduction in the number of PNMT-positive neurons in the RVLM, although the number of non-C1, spinally projecting barosensitive neurons of this area was not altered. The A5 cell group was the only other population of DβH-containing cells that was significantly depleted. The depressor response evoked by injection of tyramine into the RVLM was abolished by prior injection of toxin. The pressor response evoked by injection of glutamate into the RVLM was attenuated ipsilateral to the toxin injection but was potentiated contralateral to the toxin injection. Thus anti-DβH-saporin can be used to make selective lesions of PNMT-containing cells, allowing for the evaluation of their role in cardiovascular regulation.
Differential effects from parapyramidal region and rostral ventrolateral medulla mediated by substance P
Authors: Swiatkowski Kenneth , Dellamano Lynn M. , Vissing John , Rybicki Kenneth J. , Kozlowski Gerald P. , Iwamoto Gary A.
Published: December 2017

Rostral ventrolateral medulla (rVLM) and parapyramidal region (PPr) serve as important medullary control sites for sympathoexcitation. rVLM and PPr have direct projections to the intermediolateral cell column (IML) that are thought to be important in maintaining mean arterial blood pressure (MAP). Substance P (SP) is found in PPr neurons and in and near the subretrofacial area of the rVLM. At least some of these cells project to the IML. We investigated the involvement of SP at the IML in mediating rVLM- and PPr-evoked pressor responses in the chloralose-anesthetized cat. Pressor responses to electrical and chemical PPr and rVLM stimulation were altered after intrathecal injection, at the level of the T1-T3 spinal cord, of either SP antagonist [d-Pro2,d-Phe7,d-Trp9]-SP, SP antagonist CP 96,345, or SP antiserum. Although MAP and heart rate responses to PPr stimulation were attenuated by intrathecal SP antagonists or antiserum, MAP responses to rVLM stimulation were augmented. Previous studies have revealed differences in transmitters associated with these two areas, even though the general response of both areas is sympathoexcitatory. The present study implies that the identical substance may increase or decrease the MAP response depending on the pathway activated.
Developmental changes in renal renin mRNA half-life and responses to stimulation in fetal lambs
Authors: Wang Jinjuan , Rose James C.
Published: December 2017

In the perinatal period there is increased renin gene expression in the kidney compared with other stages of development. This may be related to changes in responsiveness of the renin gene to stimulation and/or differences in renin mRNA stability as development progresses. To ascertain if either responsiveness or stability changes in fetal life, we studied renin mRNA levels in primary cultures of renal cortical cells obtained from fetal lamb kidneys at two stages (0.7 and 0.9) of gestation after stimulation with isoproterenol, forskolin, or isobutyl methylxanthine and after inhibition of transcription with actinomycin D. Forskolin and isobutyl methylxanthine rapidly increased renin mRNA by at least twofold in the cultured cells from fetuses of both ages, with the sensitivity to stimulation higher in the cells from the mature fetal kidneys. Isoproterenol was effective only in mature fetal cells. In addition, the decay of renin mRNA after cessation of transcription was slower in mature cells compared with immature cells, the half-life being 11.6 ± 0.8 h in mature cells and 6.6 ± 0.6 h in immature cells ( P < 0.05). The data suggest that increases in both renin mRNA sensitivity to stimulation and in stability can contribute to the enhanced renin expression in the perinatal period.
Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors
Authors: Schwartz Gary J. , Whitney Andrew , Skoglund Chris , Castonguay Thomas W. , Moran Timothy H.
Published: December 2017

Adult Otsuka Long-Evans Tokushima fatty (OLETF) rats lack functional cholecystokinin A (CCK-A) receptors, are diabetic, hyperphagic, and obese, and have patterns of ingestion consistent with a satiety deficit secondary to CCK insensitivity. Because dietary fat potently stimulates CCK release, we examined how dietary fat modulates feeding in adult male OLETF rats and their lean [Long-Evans Tokushima (LETO)] controls. High-fat feeding produced sustained overconsumption of high-fat diet (30% corn oil in powdered chow) over a 3-wk period in OLETF but not LETO rats. We then assessed the ability of gastric gavage (5 ml, 1–2 kcal/ml × 15 s) or duodenal preloads (1 kcal/ml, 0.44 ml/min × 10 min) of liquid carbohydrate (glucose), protein (peptone), or fat (Intralipid) to suppress subsequent 30-min 12.5% glucose intake in both strains. In OLETF rats, gastric and duodenal fat preloads were significantly less effective in suppressing subsequent intake than were equicaloric peptone or glucose. These results demonstrate that OLETF rats fail to compensate for fat calories and suggest that their hyperphagia and obesity may stem from a reduced ability to process nutrient-elicited gastrointestinal satiety signals.
Allometric scaling of RNA, DNA, and enzyme levels: an intraspecific study
Authors: Burness Gary P. , Leary Scot C. , Hochachka Peter W. , Moyes Christopher D.
Published: December 2017

The activities of oxidative and glycolytic enzymes show body size-dependent relationships across a wide variety of taxa; however, the mechanistic basis remains unknown. We sampled white epaxial muscle from rainbow trout ( Oncorhynchus mykiss) spanning a 100-fold range in body mass. We measured activities of enzymes from aerobic and anaerobic metabolic pathways, RNA [total RNA and mRNA, pyruvate kinase (PK), citrate synthase (CS), and MyoD mRNA], and total DNA. Total RNA and DNA showed a biphasic relationship with body size, with a break point occurring after fish reached 1 yr of age. In contrast, total RNA/total DNA was constant across the entire size range. Neither CS activity nor CS mRNA levels scaled with body mass. PK activity and PK mRNA levels increased in parallel in yearling fish only ( r2= 0.91, P < 0.01). This suggests that although PK expression is transcriptionally regulated in yearlings, the molecular mechanisms regulating expression change with growth and age. This was supported by a positive correlation between MyoD and PK mRNA levels ( r2= 0.17, P < 0.05).