bluuebunny/crossref_metadata_2025 huggingface dataset:
Day length affects immune cell numbers in deer mice: interactions with age, sex, and prenatal photoperiod
Authors: Blom J. M. , Gerber J. M. , Nelson R. J.
Published: December 2017

The extent to which day length affects immune function was examined in the present study. Three goals were pursued: 1) to confirm and extend the observation that the immune systems of adult deer mice (Peromyscus maniculatus) are responsive to changes in photoperiod, 2) to examine the development of the photoperiod-associated changes in immune function, and 3) to discover whether photoperiodic information transmitted to the young during gestation influences immune function. In experiment 1, adult mice housed in short days had higher white blood cell and lymphocyte numbers than their long-day cohorts. Red blood cell and differential cell counts did not differ between long- and short-day animals. No sex differences were observed in the pattern of immune responses to photoperiod. The effect of photoperiod on immune cells in prepubertal animals was examined in experiment 2; a similar pattern of results was obtained as that for experiment 1, suggesting that the photoperiodic effect on the immune system is not mediated by sex steroid hormones. Prenatal and postnatal photoperiodic effects on immune cells were examined in experiment 3; pups gestated in one day length were cross-fostered to mothers in the same day length conditions or to mothers maintained in the alternative day length. The results of experiment 3 suggested that photoperiodic information transmitted from the mother to the young in utero subsequently affected immune systems of the pups. Animals gestated in short day lengths displayed higher immune status throughout life than mice gestated in long days. These results are discussed from an adaptive functional perspective.
Histamine H2 receptors and histidine decarboxylase in normal and leukemic human monocytes and macrophages
Authors: Mirossay L. , Chastre E. , Callebert J. , Launay J. M. , Housset B. , Zimber A. , Abita J. P. , Gespach C.
Published: December 2017

Spontaneous and all-trans-retinoic acid (RA)-induced differentiation of normal human monocytes and of leukemic THP-1 monocytes into macrophages resulted in a progressive loss of adenosine 3',5'-cyclic monophosphate production induced by histamine via typical H2 receptors (H2R). In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H2R gene fourfold, suggesting transcriptional control by a RA response element. Scatchard plots of [3H]tiotidine binding indicated the expression of H2R with similar affinity and binding capacity in THP-1 monocytes and macrophages, while the conversion of normal monocytes into macrophages decreased H2R density from 91.8 to 43.1 fmol/mg protein, with no change in affinity (Kd = 9.9 to 11.2 nM). In THP-1 macrophages, histamine inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-induced H2O2 formation via the activation of H2 receptors. Expression of the H2R gene, histamine accumulation, and histidine decarboxylase activity were also demonstrated in normal human monocytes/macrophages and peripheral lymphocytes. Histamine and H2R may therefore affect, via intracrine, autocrine, and paracrine pathways, various immune and inflammatory responses of the lymphoid and myeloid progenitors and lineages in the bone marrow and peripheral tissues.
Plasma potassium may protect sodium pumps of toad hearts from an endogenous inhibitor
Authors: Else P. L.
Published: December 2017

Resibufogenin (3-hydroxy-14,15-epoxy-20,22-dienolide glycoside) is a potent sodium pump inhibitor present in toad toxin. It is present in the skin of the cane toad (Bufo marinus) at a concentration equivalent to ouabain of approximately 1 mM. Because toads, like other amphibians, have permeable skin, resibufogenin is also found in high concentrations in the blood. In the cane toad the blood concentration is estimated to be 1 microM (D. Lichtstein, S. Kachalsky, and J. Deutsch. Life Sci. 38: 1261-1270, 1986; D. Lichtstein, S. Samuelov, J. Deutsch, H. Xu, R. A. Lutz, S. S. Chernick and S. S. Chernick. Klin. Wochenschr. 65, Suppl. 8: 40-48, 1987), a concentration thousands of times that required to produce toxicity in humans (J. S. Flier, E. Matatos-Flier, J. A. Pallotta, and D. McIsaac. Nature Lond. 279: 341-343, 1979). In examining how the cane toad avoids inhibiting its own sodium pumps, work on the heart showed that 1) cane toads possess a similar number of cardiac sodium pumps as other vertebrates, and 2) normal plasma K+ levels completely prevent ouabain, and presumably resibufogenin, from binding to cardiac sodium pumps of the cane toad. Other species, i.e., rat (Rattus norvegicus) and salamander (Ambystoma mexicanum), did not show K+ protection of their cardiac ouabain binding sites up to normal plasma K+ levels. These species do not possess the high level of endogenous ouabain-like substance found in the toad. K+ demonstrated a capacity to protect the enzymatic activity of the toad heart sodium pumps from the inhibitory effects of ouabain.
Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats
Authors: Hamelink C. R. , Currie P. J. , Chambers J. W. , Castonguay T. W. , Coscina D. V.
Published: December 2017

Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.
Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes
Authors: Williams G. , Brown T. , Becker L. , Prager M. , Giroir B. P.
Published: December 2017

Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. To determine whether NO production can be induced in skeletal muscle, we stimulated C2C12 mouse skeletal muscle myocytes with putative inducers of nitric oxide synthase (NOS). Neither lipopolysaccharide (LPS), interleukin-1 alpha (IL-1), tumor necrosis factor-alpha (TNF), nor interferon-gamma (IFN) was able to stimulate nitrite production by C2C12 cells when administered alone. However, combinations of IFN with either TNF or IL-1 resulted in significant nitrite production; simultaneous stimulation of cells with all three cytokines resulted in significantly increased nitrite production compared with any combination of two cytokines. Northern analysis of RNA obtained from stimulated C2C12 cells revealed induction of a single mRNA band that precisely coincided with the mRNA band of mouse macrophage-inducible NOS (iNOS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis followed by sequencing of the 5' 765 bases of the skeletal muscle iNOS cDNA demonstrated exact homology with mouse macrophage iNOS. These findings indicate that combinations of cytokines stimulate NO production in skeletal muscle cells via induction of the macrophage-type iNOS gene.
Role of the atrial natriuretic peptide for adrenal regulation in the teleost fish Cyprinus carpio
Authors: Kloas W. , Reinecke M. , Hanke W.
Published: December 2017

The biological role of atrial natriuretic peptide (ANP) for the adrenal tissue of the teleost fish Cyprinus carpio, the carp, was investigated using in vitro autoradiography to study ANP binding sites, immunohistochemistry to localize ANP-like peptides, and in vitro perifusion to measure adrenal cortisol and catecholamine release. 125I-labeled rat ANP-(99-126) [125I-rANP-(99-126)] binding was present in adrenal tissue exhibiting positive cooperativity with a half-maximal binding concentration (EC50) of 87 +/- 15 pM and a maximal binding capacity (Bmax) of 56 +/- 11 amol/mm2 (n = 3). 125I-rANP-(99-126) binding was competitively displaced by unlabeled ANP analogues with an intact disulfide bridge showing a lower affinity than the iodinated ligand. By the use of immunohistochemistry, ANP immunoreactivity was found in the majority of the phenylethanolamine N-methyl-transferase-immunoreactive, i.e., epinephrine-synthesizing cells. In vitro, ANP elevated both basal and acetylcholine-stimulated cortisol release by carp adrenal tissue, whereas adrenal catecholamines were significantly affected only in acetylcholine-stimulated epinephrine secretion. Thus ANP derived from the ANP-immunoreactive chromaffin cells of the carp adrenal seems to act in an autocrine and/or paracrine manner on steroidogenic interrenal and catecholaminergic chromaffin cells. Furthermore, the study indicates that the ANP effects on fish catecholamine and steroid release are reversed in mammals.
The exercise pressor reflex is attenuated by intrathecal oxytocin
Authors: Stebbins C. L. , Ortiz-Acevedo A.
Published: December 2017

We tested the hypothesis that oxytocin (Oxt) acts in the lumbar spinal cord to attenuate reflex pressor (mean arterial pressure, MAP) and heart rate (HR) responses to static hindlimb contraction (i.e., the exercise pressor reflex). Thus we compared MAP and HR responses to electrically stimulated hindlimb static contraction in the anesthetized cat before and after intrathecal injection of Oxt (30 pmol, n = 3; 300 pmol, n = 6; or 3 nmol, n = 6). The 300-pmol dose was most effective; it attenuated the pressor response to static contraction by 39 +/- 10% but had no effect on HR. In three other cats, contraction-induced increases in MAP and HR were monitored before and after intrathecal injection of 300 pmol of Oxt + 300 nmol of the selective Oxt receptor antagonist [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr9,Orn8]vasotocin. Pretreatment with the antagonist eliminated the effect of Oxt on MAP. In an additional 10 cats, increases in these same variables in response to static contraction were compared before and after intrathecal injection of the Oxt antagonist (30 nmol, n = 3 or 300 nmol, n = 7) into the lumbar spinal cord (L1-L7). Whereas 30 nmol of the Oxt antagonist had no effect, the 300-nmol dose augmented the contraction-induced pressor and HR responses by 28 +/- 7 and 32 +/- 17%, respectively. These data imply that endogenous Oxt modulates the exercise pressor reflex by its action on Oxt receptors in the lumbar spinal cord that can attenuate sensory nerve transmission from skeletal muscle.
Insulin resistance and hypertension: studies in transgenic hypertensive TGR(mREN-2)27 rats
Authors: Vettor R. , Cusin I. , Ganten D. , Rohner-Jeanrenaud F. , Ferrannini E. , Jeanrenaud B.
Published: December 2017

The link between hyperinsulinemia and hypertension is imperfectly understood. Recently, a renin gene (the mouse DBA/REN-2d gene) has been transfected into rats, leading to high blood pressure in transgene-positive animals, TGR(mREN-2)27 rats. We tested whether heterozygous hypertensive TGR(mREN-2)27 rats presented evidence of insulin resistance in comparison with the parent strain of Sprague-Dawley rats. Despite their higher blood pressure (203 +/- 8 vs. 112 +/- 6 mmHg, P < 0.001), transgenic rats had normal fasting levels of plasma glucose, insulin, free fatty acids, and triglycerides and had normal fasting rates of hepatic glucose production (by [14C]glucose infusion). During a euglycemic hyperinsulinemic clamp (3 mU/min), stimulation of whole body glucose utilization was equivalent in transgenic and control animals (12.6 +/- 0.6 vs. 10.9 +/- 1.0 mg.min-1.kg-1, respectively). Likewise, suppression of hepatic glucose output by insulin was complete in both groups. The glucose utilization index (as measured by the 2-deoxy-D-[3H]glucose technique) was similar between transgenic and control animals in several skeletal muscles (soleus, extensor digitorum longus, tibialis, diaphragm, white and red quadriceps, and white and red gastrocnemius), in white adipose tissue (periovarian and inguinal), and in brown adipose tissue. We conclude that single gene hypertension does not alter whole body and individual tissue insulin sensitivity.
Relationship between body mass, tissue metabolic rate, and sodium pump activity in mammalian liver and kidney
Authors: Couture P. , Hulbert A. J.
Published: December 2017

The allometric relationship between body mass and tissue metabolism was examined in liver and kidney cortex slices from mouse, rat, rabbit, sheep, and cattle, representing an approximately 12,000-fold difference in body mass and an 11-fold difference in mass-specific basal metabolic rate. Larger mammals have lower tissue metabolic rates (TMR; mumol O2.g wet wt-1.min-1) at 37 degrees C, yielding the equations TMR = 3.6 M-0.21 for liver slices and TMR = 3.2 M-0.11 for kidney cortex slices, where M is body mass in grams. This appears to be an intrinsic property of the tissue and is not due to differences in extracellular space or tissue protein content, because these are relatively constant in all mammalian species examined. The allometric relationships remain when tissue metabolism is expressed relative to "active cell mass" in tissue slices. Potassium uptake rate (KUR; mumol K+.g wet wt-1.min-1) was also measured (as 86Rb+ uptake) and was also lower in larger mammals, yielding the equations KUR = 1.2 M-0.14 in liver slices and KUR = 3.4 M-0.13 for kidney cortex slices. The energetic costs of sodium pump activity were estimated to be < 10% of TMR for liver and kidney cortex from all five mammalian species.
Discovery of L-162,313: a nonpeptide that mimics the biological actions of angiotensin II
Authors: Kivlighn S. D. , Huckle W. R. , Zingaro G. J. , Rivero R. A. , Lotti V. J. , Chang R. S. , Schorn T. W. , Kevin N. , Johnson R. G. , Greenlee W. J. , et al.
Published: December 2017

L-162,313 (5,7-dimethyl-2-ethyl-3-[[4-[2(n- butyloxycarbonylsulfonamido)-5-isobutyl-3-thienyl]phenyl]methyl]- imadazo[4,5-b]pyridine) is a nonpeptide that mimics the biological actions of angiotensin II (ANG II). The intravenous administration of L-162,313 increased blood pressure in the rat. The maximum increase in mean arterial pressure (MAP) was not different from the maximum response to ANG II in the same preparation. However, the duration of the pressor response after L-162,313 greatly exceeded that of ANG II. Pretreatment with ANG II receptor antagonists, L-158,809 (AT1 selective) or saralasin, blocked the L-162,313-induced increase in MAP. Enalaprilat, an angiotensin-converting enzyme inhibitor, failed to block the MAP response to L-162,313. In vitro, L-162,313-activated phosphoinositide turnover in rat aortic smooth muscle cell cultures was also blocked by L-158,809 and losartan (DuP-753). Therefore, L-162,313 is the first reported nonpeptide ANG II receptor agonist.
Potassium's cardiovascular protective mechanisms
Authors: Young D. B. , Lin H. , McCabe R. D.
Published: December 2017

High rates of potassium intake are associated with protection from cardiovascular diseases in populations consuming primitive diets and in vegetarians living in industrialized cultures. In studies in humans and in animals, a strong inverse association between potassium intake and hypertension and stroke has been described. However, acceptance of the putative protective effect has been limited by inadequate understanding of 1) long-term potassium regulation, and 2) mechanisms by which small changes in plasma potassium concentration may affect development of cardiovascular diseases. In this review, we present results from analyses of long-term potassium regulation that indicated 1) changes in potassium intake may result in potassium concentrations from 3.1 to 4.6 mmol/l, and 2) when the initial rate is below normal, potassium concentration is very sensitive to changes in potassium intake rate. In addition, we present results that provide bases for possible mechanisms by which potassium may protect against cardiovascular diseases: 1) increases in potassium inhibit free radical formation from vascular endothelial cells and macrophages; 2) elevation of potassium inhibits proliferation of vascular smooth muscle cells; 3) platelet aggregation and arterial thrombosis are inhibited by elevation of potassium; and 4) renal vascular resistance is reduced and glomerular filtration rate is increased by elevation of plasma potassium. We propose that elevation of dietary potassium intake increases plasma potassium concentration, thereby inhibiting free radical formation, smooth muscle proliferation, and thrombus formation. As a result, the rate of atherosclerotic lesion formation and thrombosis will be diminished. In addition, we propose the increase in glomerular filtration rate will cause a shift in the relationship between arterial pressure and sodium excretion that will lead to a reduction in arterial blood pressure. By these actions, high levels of dietary intake of potassium could provide the observed protection against the cardiovascular diseases that have plagued humankind since we began eating a modern high-sodium, low-potassium diet.
August Krogh Lecture. The renal concentrating mechanism in insects and mammals: a new hypothesis involving hydrostatic pressures
Authors: Schmidt-Nielsen B.
Published: December 2017

Water moves from compartments of higher to compartments of lower water potential. Osmotically active solutes and negative hydrostatic pressure both lower water potential by stretching the hydrogen bonds between water molecules (Hammel-Scholander hypothesis). In trees the negative hydrostatic pressure in the sap is balanced by the osmotic pressure of the leaves. In response to differences in water potential, water flows across biological membranes through water-filled pores. Protein molecules, aquaporins, forming hourglass-shaped pores have been identified, cloned, and located in plasma membranes in mammalian as well as other tissues. Water molecules flow single file through aquaporins. Insects concentrate the urine in the rectum. Mammals concentrate the urine in the collecting ducts in the inner medulla. In both, a compartment with a high osmotic concentration is created through ion transport. Both have a muscular coat surrounding the tissue, which shows peristaltic contractions. In insects it is the muscular layer around the rectum; in mammals it is the renal pelvic wall that surrounds the papilla. Mechanisms are proposed whereby these peristaltic contractions, through the creation of positive and negative hydrostatic pressures in the tissues, can lead to hyperosmotic excreta.
Cold acclimation-recruited nonshivering thermogenesis: the Syrian hamster is not an exception
Authors: Dicker A. , Cannon B. , Nedergaard J.
Published: December 2017

Biochemical evidence from in vitro studies of brown adipose tissue in Syrian hamsters indicates a significant degree of recruitment of the tissue as an effect of cold acclimation. However, earlier in vivo studies indicate a lack of recruitment of nonshivering thermogenesis in the intact animal as a result of cold acclimation. Because of this apparent discrepancy, the occurrence of cold acclimation-recruited nonshivering thermogenesis in hamsters was investigated. Hamsters were cold acclimated to 6 degrees C or remained at 24 degrees C (controls), and their thermogenic response was investigated in an open-circuit system at 24 degrees C. Cold acclimation resulted in a small increase in resting metabolic rate and a major increase in the thermogenic response to norepinephrine (61% increase over resting metabolic rate in controls and 156% increase in cold-acclimated animals). The absolute beta 3-specific adrenergic agonist CGP-12177 also induced a high rate of nonshivering thermogenesis, which was similarly recruited. It was concluded that, concerning the relative effect of recruitment on the capacity for nonshivering thermogenesis, the intact hamsters responded as would be predicted from in vitro experiments. Thus the hamster does not seem to constitute an exception to the general patterns described for other rodents concerning recruitment of nonshivering thermogenesis due to cold acclimation.
Blood pressures and heart rate during larval development in the anuran amphibian Xenopus laevis
Authors: Hou P. C. , Burggren W. W.
Published: December 2017

Heart rate and blood pressure were measured in lightly anesthetized developing Xenopus laevis from hatching (body mass approximately 3 mg) to the end of metamorphosis (< or = 1 g). Blood pressures in the conus arteriosus, truncus arteriosus, and ventricle were measured by a servo-null micropressure system. Heart rate was determined from blood pressure recordings, and cardiac cycles were videotaped through a dissecting microscope. Heart rate varied from 50 to 150 beats/min and showed a negative correlation with body mass, with a slope less than predicted from allometric equations based on adult vertebrates. Mean truncus pressures showed a positive correlation with body mass, increasing from 4 mmHg in a 25-mg larva to 9 mmHg in a 1-g larva. The pressure waveform during ventricular systole was similar in all developmental stages examined, whereas those in conus and truncus varied with development. Conus pressures differed distinctly from truncus pressure during diastole in all larvae examined, suggesting the existence of functional valves between conus and truncus as early as stage 46 of the Nieuwkoop-Faber larval staging system. Although the developmental patterns of heart rate and blood pressure in X. laevis showed significant correlation with body mass, body mass explained less than one-half of the variation in these variables. Therefore developmental factors other than body mass, such as changes in heart mass and the addition of new resistance vessels, may influence heart rate and blood pressure during development in X. laevis.
Alterations in extracellular GABA in the ventral hypothalamus of rats in response to acute glucoprivation
Authors: Beverly J. L. , Beverly M. F. , Meguid M. M.
Published: December 2017

gamma-Aminobutyric acidergic (GABA) mechanisms in the ventral hypothalamus may be involved in counterregulatory responses to glucoprivic episodes. Microdialysis probes (1 mm) were placed into the ventromedial hypothalamus (VMH) or lateral hypothalamus (LHA) of male Sprague-Dawley rats 3.5 h before 2-deoxy-D-glucose (2-DG) administration (200 mg/kg i.v.). Probes were perfused (2 ml/min) with Ringer solution, and samples were collected every 10 min from 30 min before to 60 min after 2-DG. By 30 min after 2-DG, GABA concentration in VMH dialysate increased in a bimodal fashion to 204 +/- 36% (P < 0.01) of baseline, and GABA concentration in LHA dialysate decreased to 77 +/- 4% (P < 0.01) of baseline. The changes in dialysate GABA concentrations occurred concurrently with the animals eating and returned to baseline by 60 min. When animals were denied access to food after 2-DG, the decrease in LHA GABA was not apparent and VMH GABA remained approximately 15% above baseline at the end of the sample period. The results of the present study provide evidence that GABAergic systems in the ventral hypothalamus are responsive to alterations in glucose status.
Neuronal discharge of preoptic/anterior hypothalamic thermosensitive neurons: relation to NREM sleep
Authors: Alam M. N. , McGinty D. , Szymusiak R.
Published: December 2017

Thermosensitive neurons of the preoptic/anterior hypothalamic area (POAH) have been implicated in the regulation of non-rapid eye movement (NREM) sleep. We attempted to identify those medial POAH thermosensitive neurons that may be involved in NREM sleep regulation. The thermosensitivity of medial POAH neurons was studied in five freely moving adult cats by local cooling or warming of the medial POAH with a water-perfused thermode. Of 308 neurons, 65 (21%) were classified as thermosensitive, including 31 (10%) warm-sensitive and 34 (11%) cold-sensitive neurons. The spontaneous discharge rates of 28 warm-sensitive, 34 cold-sensitive, and 115 randomly selected thermoinsensitive neurons were recorded through one to three sleep-waking cycles. Patterns of spontaneous activity for warm- and cold-sensitive neurons were different. Of 28 warm-sensitive neurons, 18 (64%) exhibited increased discharge rate during NREM sleep compared with waking (NREM/wake, > or = 1.2). This subpopulation of warm-sensitive neurons also exhibited significantly increased thermosensitivity when tested during NREM sleep. Of 34 cold-sensitive neurons, 25 (74%) discharged more slowly during NREM sleep compared with waking (NREM/wake, < or = 0.8). This subpopulation of cold-sensitive neurons exhibited decreased thermosensitivity during NREM sleep. These results are consistent with a hypothesis that the activation of sleep-related warm-sensitive neurons and the deactivation of wake-related cold-sensitive neurons may play a key role in the onset and regulation of NREM sleep.
Role of high-affinity folate-binding protein in the plasma distribution of tetrahydrofolate in pigs
Authors: Sasaki K. , Natsuhori M. , Shimoda M. , Saima Y. , Kokue E.
Published: December 2017

Stability and protein-binding properties of tetrahydrofolate (THF) in pig plasma were studied in vitro. THF in plasma was stable for more than 120 min when it existed in a bound form, whereas THF both in plasma ultrafiltrate and in plasma ultrafiltrate plus porcine albumin was degraded rapidly and disappeared soon after its addition. These results suggest that high-affinity folate-binding protein (HFBP) is related to the stability of THF. THF-protein binding kinetic analysis showed that porcine plasma had HFBP and low-affinity binding protein (albumin) for THF. Dissociation constant and maximal binding capacity of HFBP were calculated to be 0.4 and 70 nM, respectively, indicating that > 98% of endogenous plasma THF existed in bound form with HFBP. Porcine albumin was not essentially a protein that binds and protects endogenous THF from degradation. We conclude that most endogenous THF binds to HFBP and only the unbound form of THF is rapidly degraded in pig plasma. HFBP protects THF from degradation and allows THF to exist stably in pig plasma. In addition, HFBP may govern the species specificity of plasma folate distribution in pigs.
Changes in the apical surface of chloride cells following acclimation of lampreys to seawater
Authors: Bartels H. , Moldenhauer A. , Potter I. C.
Published: December 2017

Scanning electron microscopy (SEM) was used to study the changes that occur in the morphological relationships between chloride and pavement cells in the gills during acclimation of young adult lampreys to seawater. Because chloride cells are located predominantly between lamellae and are thus obscured from view, the lamellae were removed with the use of a micromanipulator installed in a SEM. In gills of animals maintained in river water, chloride cells could then be seen to be dislike and typically to form single rows between successive lamellae. After acclimation to seawater, the apical surfaces of chloride cells lose their microvilli and change in shape from small circles to rectangles that extend the full width between successive lamellae. These changes result in an increase in the length of the paracellular pathway between chloride cells. Previous work has shown that the number of strands of the zonulae occludentes sealing this pathway declines under these conditions. This presumably leads to an increase in paracellular permeability of the gill epithelium, thereby providing the low-resistance paracellular shunt required for the passive movement of sodium into the environment during osmoregulation in seawater. The above changes are reversed by transfer of lampreys downward to 10% seawater.
Lymphatic pump function curves in awake sheep
Authors: Drake R. E. , Dhother S. , Oppenlander V. M. , Gabel J. C.
Published: December 2017

We determined the relationship between flow rate and inflow pressure for intestinal lymphatic vessels in six sheep. First we anesthetized the sheep and cannulated both ends of a 6- to 10-cm-long segment of intestinal lymphatic. We allowed the sheep to recover from the anesthesia for 2-24 h. To determine the flow rate-inflow pressure relationship, we recorded the inflow pressure and infused Ringer solution into the lymphatic at rates from 34 to 510 microliters/min. The flow rate-pressure relationship was not linear and it had two regions. For flow rates less than approximately 150 microliters/min, inflow pressure was greater than outflow pressure. Thus the lymphatic pumped fluid against a pressure gradient. For flow rates > 150 microliters/min, inflow pressure was greater than outflow pressure, and we attributed most of the flow to the favorable inflow-outflow pressure gradient (passive flow). When we used verapamil to inhibit lymphatic pumping, we found no flow for inflow pressure less than outflow pressure, and flow increased linearly for inflow pressure greater than outflow pressure. Our data for actively pumping lymphatic vessels are consistent with the flow vs. pressure relationships derived from mathematical models of the lymphatic pump. Furthermore, our data with verapamil confirm that active lymphatic pumping was responsible for the nonlinear flow vs. pressure relationship for the lymphatic vessels.
Thermoregulatory and heat-shock protein response deficits in cold-exposed diabetic mice
Authors: Matz J. M. , LaVoi K. P. , Epstein P. N. , Blake M. J.
Published: December 2017

Cold-induced expression of heat-shock proteins (HSPs) has been suggested to facilitate thermogenesis in brown adipose tissue (BAT). However, the regulation of this response and the mechanism supporting this facilitation have not been established. Because of the significant role of insulin in maintaining BAT thermogenesis, we employed a transgenic mouse model of diabetes to investigate the regulation and function of HSPs in BAT thermogenesis. These transgenic mice overexpress a calmodulin minigene regulated by the rat insulin II promotor, resulting in severe diabetes characterized by elevated blood glucose and glucagon that coincides with reduced serum and pancreatic insulin. Body temperature (Tb) of diabetic mice dropped significantly faster during a 3-h cold exposure (6 degrees C) than Tb of similarly treated control littermates. Cold exposure resulted in increased levels of constitutive and inducible HSP70 transcripts in control mice, but only constitutive HSP70 mRNA transcripts were induced in diabetic mice. Diabetes did not affect uncoupling protein induction, but cold-induced expression of members of other HSP families was reduced. Correspondingly, heat-shock regulatory factors were not activated in diabetic mice even though these factors were present. Phenylephrine induced HSP70 expression in control and diabetic animals, indicating that alpha-receptor-coupled HSP induction remained intact in BAT of diabetic mice. Insulin replacement restored the Tb response of diabetic mice as well as the HSP response. From these results it is clear that physiological signals that regulate cold-induced activation of BAT also regulate HSP expression in this tissue. This diabetic model provides a novel system in which the HSP response to cold has been selectively knocked out, making it a useful tool for the study of HSP regulation and function in BAT.
Abdominal surgery-induced inhibition of gastric emptying is mediated in part by interleukin-1 beta
Authors: Coimbra C. R. , Plourde V.
Published: December 2017

The role of interleukin-1 beta (IL-1 beta) in abdominal surgery-induced inhibition of gastric emptying was investigated. Abdominal surgery was performed under halothane anesthesia, and 5 min later, the 20-min rate of gastric emptying was measured by the phenol red method in conscious animals. In nonoperated animals, intravenous IL-1 beta dose dependently decreased gastric emptying from 55.1 +/- 1.7% in controls to 8.0 +/- 3.5% (P < 0.05) after treatment with 1 microgram IL-1 beta. Prior administration of IL-1 beta receptor antagonist (IL-1 beta ra; 200 micrograms) completely abolished the inhibitory effects of IL-1 beta. Surgery inhibited gastric emptying by 83.4% compared with rats receiving anesthesia alone. IL-1 beta ra (200 micrograms) reversed the inhibition of gastric emptying by 34.8% (P < 0.05) in the early (30 min) postoperative period and by 32.3% (P < 0.05) in the late (120 min) postoperative period. Use of calcitonin gene-related peptide-(8-37) [CGRP-(8-37)] in combination with IL-1 beta ra in operated animals resulted in no further reversal in the inhibition of gastric emptying: CGRP-(8-37)-treated animals = 42.1 +/- 4.1%; CGRP-(8-37) + IL-1 beta ra = 38.0 +/- 4.4% (not significant). Moreover, in nonoperated animals, CGRP-(8-37) completely abolished the effects of intravenous IL-1 beta on gastric emptying: IL-1 beta-treated animals = 11.1 +/- 2.0%; IL-1 beta + CGRP-(8-37) = 40.6 +/- 6.4% (P < 0.05). These results suggest that IL-1 beta is mediating part of the gastric ileus observed after abdominal surgery through the release of CGRP from the visceral afferents.
Characterization and function of ATP receptors on hepatocytes from the little skate Raja erinacea
Authors: Nathanson M. H. , Mariwalla K.
Published: December 2017

Hormonal regulation of hepatocytes, via cytosolic Ca2+ signaling, is well established in higher life forms but has not been investigated in elasmobranchs. We therefore examined Ca2+ signaling in hepatocytes isolated from the little skate, Raja erinacea. In hepatocyte populations, ATP induced a rapid, biphasic increase in Ca2+, as it does in mammalian hepatocytes. Other hormones that act on mammalian hepatocytes, such as vasopressin, angiotensin, and phenylephrine, induced no such Ca2+ increase. The initial phase of the ATP-induced Ca2+ increase was seen even in Ca(2+)-free medium, whereas the late sustained phase of the increase was not. Similar dose-response curves were obtained by stimulation with ATP, ADP, UTP, and 2-methylthio-ATP. In contrast, AMP, adenosine, beta, gamma-methyl-ATP, CTP, and GTP induced little or no Ca2+ increase. In single hepatocytes, ATP, ADP, UTP, and 2-methylthio-ATP each induced a sustained increase in Ca2+ at high concentrations, but at low concentrations induced Ca2+ oscillations. A maximal concentration of ATP (100 microM) caused a marked, transient increase in bile flow in the isolated perfused skate liver, whereas 100 microM adenosine had no such effect. These findings demonstrate that skate hepatocytes possess P2 nucleotide receptors that link to intracellular plus extracellular Ca2+ mobilization, which in turn regulates bile secretion. The broad specificity of the response to ATP and related compounds suggests either that multiple types of P2 receptors are expressed by skate hepatocytes or else that these cells possess a single primitive nucleotide receptor from which other P2 subtypes subsequently evolved.
Effect of interleukin-1 beta on EEG power density during sleep depends on circadian phase
Authors: Lancel M. , Mathias S. , Faulhaber J. , Schiffelholz T.
Published: December 2017

The cytokine interleukin (IL)-1 is a key mediator of the somnogenic response to immune challenge. In this vehicle-controlled study we evaluated circadian interference with the sleep-promoting effects of IL-1 beta. In two randomized experiments, rats were injected intracerebroventricularly with 5 ng IL-1 beta either at the beginning of the rest phase or at the beginning of the activity phase. Recordings were made during the 24 h preceding the injections (baseline) and during the first 12 postinjection hours. To avoid masking effects of light, the rats were maintained under a skeleton photoperiod during recording. During both the rest and activity phase, IL-1 beta induced fever and initially promoted non-rapid eye movement sleep (REMS). The effect of IL-1 beta on the duration of non-REMS and electroencephalogram (EEG) power densities within non-REMS was related to circadian phase. During the rest phase, IL-1 beta resulted in a minor increase in non-REMS duration but a prominent enhancement in EEG activity in the delta (0.5-4 Hz) and most other frequency bands. During the activity phase, IL-1 beta evoked a larger increase in the duration of non-REMS but hardly affected EEG activity within this state. Thus the effects of IL-1 beta on non-REMS are strongly influenced by diurnal phase. The alterations in EEG power density are in contrast to those elicited by sleep deprivation, which are largely independent of time of day. It is concluded that IL-1 beta activates EEG regulatory mechanisms mediated by processes that depend on circadian phase.
Macrovascular dopamine release
Authors: Kraschinski S. , Epple A. , Nibbio B.
Published: December 2017

In an animal model, the American eel, perifused elastic arteries and large veins, but not the heart and organs with extensive microvascular supply (gills and opisthonephric kidney), release spontaneously free dopamine. Only the region of the cardinal vein, which contains the adrenomedullary equivalent, also releases norepinephrine (NE) and epinephrine (E). Ca2+, KCl, and E stimulate dopamine release from the ventral aorta and caudal vein, indicating that this phenomenon is due to secretion and not to washout. E also stimulates NE release from the ventral aorta and caudal vein. In the rat, both aorta and vena cava spontaneously release dopamine and NE. Thus dopamine secretion from large blood vessels may be general in vertebrates. The dopamine response to high physiological concentrations of E in vivo and in vitro suggests that macrovascular dopamine may be involved in local stress responses.
Selective hypoglycemia in the liver induces adrenomedullary counterregulatory response
Authors: Lamarche L. , Yamaguchi N. , Peronnet F.
Published: December 2017

The present study was designed to investigate adrenal medullary responses to a selective regional hypoglycemia in the liver of dogs with hepatic cross-perfusion. The liver of recipient dogs (Rc) was perfused with vena caval and aortic blood of donor dogs (Dn) through the portal vein and hepatic artery, respectively. Total hepatic venous blood of Rc was returned to Dn through the left jugular vein. Upon the cross-perfusion, glucose (Glc, 5%) was infused at an average rate of 3.5 +/- 0.2 mg.kg-1.min-1 (n = 12) in Rc to compensate the loss of hepatic Glc delivery into the systemic circulation. Insulin (5.0 IU/kg i.v.) was administered to Dn followed by infusion with an average rate of 0.95 +/- 0.17 IU kg-1.min-1 (n = 6), and this served as the hepatic hypoglycemic group. Saline was similarly administered to Dn, which served as the normoglycemic control group. In the hepatic hypoglycemic group, aortic and vena caval Glc levels in Dn, which represent Glc concentrations entering the liver of Rc, decreased from 129.9 +/- 7.1 and 122.5 +/- 7.8 to 44.6 +/- 6.1 and 38.0 +/- 5.9 mg/dl (P < 0.05) 45 min after insulin administration, respectively. During this regional hepatic hypoglycemia in Rc, the systemic glycemia being kept within a normal range, adrenal epinephrine and norepinephrine output increased from 245.5 +/- 55.8 and 39.1 +/- 9.9 to 618.9 +/- 180.4 and 134.3 +/- 52.7 ng/min (P < 0.05), respectively. By contrast, aortic Glc and insulin levels in Dn of the normoglycemic control group remained unchanged, as did adrenal epinephrine and norepinephrine output in Rc. The results indicate that the regional hepatic hypoglycemia can significantly increase adrenal catecholamine secretion even during systemic (central) normoglycemia. The study suggests that the hepatoadrenal Glc counter-regulatory reflex may be functionally implicated in insulin-induced hypoglycemia.
Neutral endopeptidase modulates VIP-induced vasodilation in hamster cheek pouch vessels in situ
Authors: Suzuki H. , Gao X. P. , Olopade C. O. , Rubinstein I.
Published: December 2017

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP) dilates resistance arterioles in the in situ systemic circulation and whether inhibitors of neutral endopeptidase (NEP) and angiotensin I-converting enzyme (ACE), two membrane-bound metalloenzymes that are widely distributed in the microcirculation and cleave and inactive VIP, potentiate this response. Using intravital microscopy, we found that VIP (0.05 and 0.1 nmol) induced significant vasodilation in the hamster cheek pouch (13 +/- 1 and 20 +/- 2% increase from baseline, respectively; mean +/- SE; P < 0.05). These responses were significantly potentiated by topical application of phosphoramidon and thiorphan, two relatively selective NEP inhibitors, but not by captopril, a relatively selective ACE inhibitor. Furthermore, suffusion of a mixture of proteinase inhibitors consisting of leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid to inhibit serine proteinases, including mast cell tryptase, aminopeptidases, and carboxypeptidase N, respectively, had no significant effects on VIP-induced responses. These data indicate that VIP elicits vasodilation in the in situ systemic microcirculation and that NEP modulates this response.
Decreased muscle GLUT-4 and contraction-induced glucose transport after eccentric contractions
Authors: Kristiansen S. , Asp S. , Richter E. A.
Published: December 2017

Eccentric exercise causes muscle damage and decreased muscle glycogen and glucose transporter isoform (GLUT-4) protein content. We investigated whether the contraction-induced increase in skeletal muscle glucose transport and muscle performance is affected by prior eccentric contractions. The calf muscles from rats were stimulated for eccentric (EC) or concentric (CC) contractions or were passively stretched (ST). Muscles from unstimulated control (CT) rats were also studied. Two days later, all rats had their isolated hindlimbs perfused either at rest or during 15 min of isometric muscle contractions. EC rats had a significantly lower total GLUT-4 protein content in the white gastrocnemius (GW) muscle (55%) and red gastrocnemius (GR) muscle (34%) compared with muscle from the CT, ST, and CC rats. In contrast, GLUT-1 protein content was approximately twofold higher in the GW muscle in EC rats than in CT rats. In the GW and GR muscle, prior eccentric exercise decreased contraction-induced stimulation of glucose transport compared with CT, ST, and CC rats despite no difference in tension development and oxygen uptake among the groups. There was no change in total GLUT-4 content and glucose transport in the soleus (S) muscle among the four group. It is concluded that the GLUT-4 and GLUT-1 protein contents in fast-twitch muscle are decreased and increased, respectively, 2 days after eccentric contractions. The functional consequence of these changes appears to be decreased contraction-induced increase in skeletal muscle glucose transport.
Contribution of ANP to plasma protein escape during VE: effects of thiorphan and atrial appendectomy
Authors: Tucker V. L.
Published: December 2017

The effects of endopeptidase inhibition and right atrial appendectomy (AA) on plasma immunoreactive atrial natriuretic peptide (irANP) concentrations and extravascular accumulation of 131I-labeled bovine serum albumin (CBSA) during volume expansion (VE) were examined in pentobarbital sodium-anesthetized rats (n = 5 per group). Compared with controls, infusion of isoncotic albumin (30 ml/kg) increased central venous pressure (CVP) by 5.5 mmHg, plasma irANP by 7-fold, and CBSA in multiple tissues by 1.6- to 4-fold (P < or = 0.05). Inhibition of ANP metabolism with thiorphan (40 mg/kg) had no effect in control animals but increased plasma irANP (+118%) and CBSA (+30-100%) compared with VE alone (P < or = 0.05). Likewise, interference with ANP release by AA reduced plasma irANP (-80%) and CBSA (-30 to -80%) response to VE in parallel (P < or = 0.05). The peak increase in CVP during VE was not affected by either of these manipulations. It is concluded that endogenous ANP increases plasma protein extravasation independent of volume and pressure disturbances during acute intravascular expansion.
Central effects of morphine and morphine-6-glucuronide on tissue protein synthesis
Authors: Hashiguchi Y. , Molina P. E. , Preedy V. R. , Sugden P. H. , McNurlan M. A. , Garlick P. J. , Abumrad N. N.
Published: December 2017

The central and peripheral effects of morphine sulfate (Mor) and morphine-6-glucuronide (M6G) on the fractional rates of tissue protein synthesis (kappa s) were determined. We determined ks in conscious rats 2 h after intracerebroventricular injection of Mor (80 micrograms/rat), M6G (1 microgram/rat), or H2O (5 microliters). Intracerebroventricular Mor and M6G administration decreased ks in the liver by 19 and 18% spleen by 19 and 17%, and gastrocnemius by 18 and 17%, respectively. Intravenous injection of Mor (8 mg/kg) or M6G (0.4 mg/kg) did not affect ks in any of the tissues studied. Intracerebroventricular Mor and M6G resulted in an equivalent 10- to 15-fold increase in plasma epinephrine, 2- to 3-fold increase in norepinephrine, and 80-90% increase in corticosterone, with no change in insulin levels. Intracerebroventricular Mor produced a significant 30% decrease in arterial partial O2 pressure (PaO2) and no significant changes in arterial pH and arterial partial CO2 pressure (PacO2). Intracerebroventricular M6G decreased PaO2 (40%) and pH (from 7.44 +/- 0.01 to 7.34 +/- 0.02) and increased Paco2 (36%). The potential contribution of hypoxia to the opiate-induced decrease in ks was assessed in an additional set of rats exposed to 5% O2-95% N2. One or 2 h of hypoxia decreased protein synthesis in the brain by 47 and 56%, liver by 69 and 69%, and skeletal muscle by 51 and 52%, respectively. Our results indicate that Mor and M6G suppress tissue protein synthesis through central mechanisms, most likely mediated by opiate-induced respiratory depression in association with neural and hormonal alterations.