bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroxisomal beta-oxidation is a significant pathway for catabolism of fatty acids in a marine teleost
Authors: Crockett E. L. , Sidell B. D.
Published: December 2017

Hepatic beta-oxidation is characterized in a marine teleost, Myoxocephalus octodecimspinosus, to determine mitochondrial and peroxisomal substrate selectivity as well as metabolic partitioning. Substrate selectivity is broad for peroxisomal beta-oxidation. Acyl CoA oxidase activities, with all unsaturated substrates measured, are at least 35% of activity with palmitoyl CoA (16:0), a saturated substrate. Mitochondrial selectivities are more pronounced. Carnitine palmitoyltransferase activity with a monounsaturate, palmitoleoyl CoA (16:1), is nearly 40% greater than activity with palmitoyl CoA, whereas activities with two polyunsaturates are < 10% of activity with the saturate. The presence of polyunsaturated acyl CoA esters inhibits up to 70% the oxidation of palmitoyl CoA by intact peroxisomes. Acyl CoA hydrolase activity is localized to peroxisomal fractions prepared by density-gradient centrifugation. Hydrolytic activity in these fractions is nearly twofold the activity of beta-oxidation. Estimates for metabolic partitioning suggest that at least 50% of hepatic beta-oxidation may be initiated by the peroxisomal compartment.
Arterial pulse pressure and vasopressin release in humans during lower body negative pressure
Authors: Norsk P. , Ellegaard P. , Videbaek R. , Stadeager C. , Jessen F. , Johansen L. B. , Kristensen M. S. , Kamegai M. , Warberg J. , Christensen N. J.
Published: December 2017

The hypothesis was tested that narrowing of arterial pulse pressure (PP) is a determinant of arginine vasopressin (AVP) release in humans. Six normal males completed a two-step lower body negative pressure (LBNP) protocol of -20 and -50 mmHg, respectively, for 10 min each. None of these subjects experienced presyncopal symptoms. Arterial plasma AVP and plasma renin activity (PRA) (at 2-min intervals) only increased subsequent to a decrease in PP (invasive brachial arterial measurements) and stroke volume (ultrasound Doppler technique, n = 4). Simultaneously, mean arterial pressure did not change. A selective decrease in central venous pressure and left atrial diameter (echocardiography, n = 4) at LBNP of -20 mmHg did not affect AVP or PRA, whereas arterial plasma norepinephrine increased (n = 4). During LBNP, significant (P < 0.05) intraindividual linear correlations were observed between log(AVP) and PP in four of the subjects with r values from -0.75 to -0.99 and between log(PRA) and PP in all six subjects with r values from -0.89 to -0.98. In conclusion, these results are in compliance with the hypothesis that narrowing of PP in humans during central hypovolemia is a determinant of AVP and renin release.
Role of the spinal cord in generating the 2- to 6-Hz rhythm in rat sympathetic outflow
Authors: Allen A. M. , Adams J. M. , Guyenet P. G.
Published: December 2017

In baroreceptor-denervated animals, sympathetic nerve discharge (SND) displays a 2- to 6-Hz rhythm. Current theories suggest that this rhythm is generated by a neural oscillator in the medulla. In urethan-anesthetized rats, we have examined the effect on the 2- to 6-Hz rhythm of lumbar SND produced by 1) altering the firing pattern of a major output of this medullary network [the rostral ventrolateral medulla (RVLM)] and 2) disrupting the interactions between medulla and spinal cord (SC). Microinjection of muscimol [gamma-aminobutyric acid (GABA) agonist] unilaterally or a mixture of kynurenic acid (KYN; broad spectrum, excitatory amino acid antagonist) and bicuculline (GABAA antagonist) bilaterally into RVLM produced little effect on the 2- to 6-Hz rhythm. Intrathecal injection of KYN or transection of the cervical SC also had little effect once SND had been restored by intrathecal injection of kainic acid (excitatory amino acid agonist). Thus, whereas an excitatory input to the spinal cord is required for the generation of basal SND, patterning of this input is not critical for production of the 2- to 6-Hz SND rhythm that, in this species, may be essentially of spinal origin.
Bafilomycin-sensitive acid secretion by mantle epithelium of the freshwater clam, Unio complanatus
Authors: Hudson R. L.
Published: December 2017

This study reports the effects of a series of putative inhibitors of proton translocation on electrogenic acid secretion by the isolated shell-facing mantle epithelium of the freshwater clam, Unio complanatus. In this epithelium, adenosine 3',5'-cyclic monophosphate (cAMP)-dependent acid secretion is electrogenic and equivalent to the cAMP-dependent short-circuit current (Isc) when mounted in a Ussing-type flux chamber. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPases (V-type ATPases), inhibited cAMP-dependent electrogenic acid secretion, with an IC50 of 7 nM and a maximum effect at 100 nM. Inhibition of acid secretion by bafilomycin A1 occurred only when added to the shell side and was not reversed by repeated washings. Concomitant with the inhibition of cAMP-dependent Isc by bafilomycin A1, the electrical potential difference across the shell-facing membrane depolarized, and the conductance ratio of the apical to basolateral membranes decreased. The cAMP-dependent Isc and cAMP-dependent acid secretion also were inhibited by dicyclohexyl-carbodiimide, diethylstilbestrol, N-ethylmaleimide, and tributyltin. Amiloride, omeprazole, oligomycin, venturicidin, and ouabain had no effect on either cAMP-dependent Isc or cAMP-dependent acid secretion. The cAMP-dependent Isc and cAMP-dependent acid secretion were not affected by Na(+)-free or K(+)-free solutions. Finally, the cAMP-dependent Isc was strongly dependent on the pH of the shell-facing compartment, with 50% inhibition of the maximum cAMP-dependent Isc occurring at pH 6.0 and complete inhibition at pH 5.5.(ABSTRACT TRUNCATED AT 250 WORDS)
Noncholinergic, nonadrenergic cortical vasodilatation elicited by thalamic centromedian-parafascicular complex
Authors: Goadsby P. J. , Seylaz J. , Mraovitch S.
Published: December 2017

The centromedian-parafascicular complex (CMPf) of the intralaminar thalamus was stimulated in anesthetized, ventilated rats, and cerebral cortical perfusion was continuously measured using laser Doppler flowmetry. Stimulation led to a frequency- and intensity-dependent increase in cortical perfusion (vasodilatation). The maximum response was seen at a rate of 200/s, and studied at 150 microA, was a 120 +/- 27% (n = 6) increase in flow. The mean time from the initiation of stimulation to a change in the cerebral blood flow measured by laser Doppler flowmeter signal was 800 +/- 100 ms (n = 13). The response to electrical stimulation was not blocked after high spinal cord section. Chemical stimulation of the CMPf neurons by microinjection of carbachol led to a 98 +/- 15% (n = 4) increase in flow. The response to electrical stimulation was not blocked by the muscarinic antagonist scopolamine (1 mg/kg) or by the nicotinic antagonist mecamylamine (4 mg/kg). It was also unaffected by the beta-adrenoceptor antagonist propranolol (1.5 mg/kg). These data add to understanding of the CMPf cerebral vasodilator response by demonstrating a robust stimulus-locked change in cortical perfusion that does not involve a cholinergic or adrenergic mechanism. It is also shown to be frequency and intensity dependent, consistent with a functioning physiological system, and has a rapid onset consistent with a primarily neurally mediated phenomenon. Furthermore, it is elicited by pathways that may possibly be entirely within the central nervous system and is due to activation of cell bodies within the region.
Ca2+ transport pathways in brush-border membrane vesicles of crustacean antennal glands
Authors: Ahearn G. A. , Franco P.
Published: December 2017

Calcium uptake by brush-border membrane vesicles of Atlantic lobster (Homarus americanus) kidneys (antennal glands) in independent experiments was stimulated by outwardly directed Na or H gradients. In the absence of external amiloride, 45Ca uptake was strongly stimulated by an outwardly directed Na gradient, and this stimulation was enhanced by the addition of an inside-negative membrane potential. External amiloride (2 mM) reduced 45Ca uptake sixfold and lowered sensitivity to membrane potential. 45Ca influx kinetics (2.5-s uptake) in the presence of an outwardly directed H gradient and inside-negative membrane potential were composed of three components: 1) an amiloride-sensitive carrier system, 2) an amiloride-insensitive carrier system, and 3) a verapamil- and membrane potential-sensitive process that may represent diffusional transfer through a calcium channel. It was concluded that 45Ca entry by the amiloride-sensitive process occurred by a previously described electrogenic 2 Na-1 H antiport mechanism [Ahearn, G., and L. Clay. Am. J. Physiol. 257 (Regulatory Integrative Comp. Physiol. 26): R484-R493, 1989; Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28): F758-F767, 1990; Ahearn, G., P. Franco, and L. Clay. J. Membr. Biol. 116: 215-226, 1990]. 45Ca influx by the amiloride-insensitive mechanism occurred by an apparent electroneutral 1 Ca-2 Na exchange. Transport stoichiometry of the latter mechanism was tentatively established by experiments determining intravesicular Na binding properties and by its apparent lack of response to a membrane potential. At physiological Na, Ca, and H concentrations in the antennal gland lumen and epithelial cytosol, these three calcium transport pathways individually may make significant contributions to net calcium reabsorption to the blood.
Ascorbic acid transport by intestinal brush-border membrane vesicles of the teleost Anguilla anguilla
Authors: Maffia M. , Ahearn G. A. , Vilella S. , Zonno V. , Storelli C.
Published: December 2017

Transport of L-ascorbate by intestinal brush-border membrane vesicles of European eel Anguilla anguilla was stimulated by a transmembrane Na gradient (out > in) but not by a similarly directed gradient of K. Under short-circuited membrane potential conditions, a kinetic analysis of L-ascorbate influx indicated the presence of a single Na-dependent carrier process (Kapp = 0.75 +/- 0.07 mM and Jmax = 0.33 +/- 0.03 nmol.mg protein-1.min-1) and a nonsaturable transfer component with an apparent diffusional permeability (P) of 0.27 +/- 0.02 microliter.mg protein-1.min-1. D-Isoascorbate was a competitive inhibitor of L-ascorbate influx exhibiting a Ki of 8.21 +/- 0.63 mM. The electrogenic nature of +Na-L-ascorbate cotransport was confirmed by a stimulatory effect of an inside-negative membrane potential on vitamin uptake. Hill analysis of L-ascorbate influx over a wide range of external Na concentrations suggested a 2 Na-to-1 L-ascorbate binding ratio. Results indicate that the vitamin L-ascorbate is transported across fish intestinal brush-border membranes by an electrogenic Na-dependent carrier process in conjunction with more than one sodium ion.
Inhibition of chemoreceptor inputs to nucleus of tractus solitarius neurons during baroreceptor stimulation
Authors: Mifflin S. W.
Published: December 2017

The reflex effects of arterial chemoreceptor activation are attenuated as arterial pressure is elevated and augmented as arterial pressure is decreased. This study was designed to test the hypothesis that excitatory arterial chemoreceptor inputs to neurons in the nucleus tractus solitarius (NTS) are inhibited by arterial baroreceptors. In pentobarbital sodium-anesthetized, mechanically ventilated, paralyzed cats, extracellular recordings were obtained from NTS neurons, which were excited after brief activation of ipsilateral carotid body chemoreceptors. During increases in arterial pressure, carotid sinus nerve (CSN)-evoked discharge was 45-112% of the control-evoked discharge at the prevailing level of arterial pressure (n = 70). Inhibition of CSN-evoked discharge during increased arterial pressure was significant when evoked discharge was < 90% of control (n = 31; 67 +/- 2%, mean percent of control-evoked discharge +/- SE; P < 0.01, Wilcoxon signed-rank test). The inhibition of CSN-evoked discharge was reduced after section of both vagi, both aortic nerves, and the contralateral CSN (n = 5, P < 0.05). These results demonstrate that activation of arterial baroreceptors attenuates excitatory chemoreceptor inputs to a subpopulation of NTS neurons. The inhibition appears to be mediated by disfacilitation. The results indicate that baroreceptor modulation of arterial chemoreflexes occurs at an early stage of the reflex arc, within the NTS. The results also suggest that sympathoinhibition evoked by baroreceptors might include, as a component, reduced sympathoexcitatory, i.e., chemoreceptor, drive.
Possible involvement of brain oxytocin in modulating vasopressin antipyretic action
Authors: Poulin P. , Pittman Q. J.
Published: December 2017

Experiments were undertaken to test whether oxytocin (OT) may modulate the antipyretic action of arginine vasopressin (AVP) and to determine whether the action of endogenously released OT and/or AVP evoked by fever may modulate the motor actions of exogenous AVP. Intracerebroventricular (icv) injection of interleukin-1 alpha (IL-1 alpha, 40 ng) elicited a significantly attenuated rise in body temperature during the 2nd h of the febrile responses in OT-pretreated (0.1-10 pmol icv, 24 h earlier) rats. At the end of the 2nd h, administration of AVP (1 pmol icv), but not OT (10 pmol icv), significantly suppressed the febrile response in OT-pretreated but not in saline-pretreated rats. In nonfebrile OT-pretreated rats, 10 but not 1 pmol of AVP (icv) caused a significant decrease in body temperature. In rats pretreated with IL-1 alpha (40 ng icv) injection of AVP (100 pmol icv) induced enhanced motor responses. In summary, the ability of OT pretreatment to alter the febrile response to IL-1 alpha and the antipyretic action of AVP suggests a role for this peptide in fever. Furthermore, the observation that fever pretreatment can lower the threshold for convulsive-like behavior evoked by subsequent exposure to AVP raises the possibility that central OT and/or AVP released during fever could play a role in the genesis of febrile convulsions.
Cerebrovasodilation elicited by fastigial stimulation is preserved under deep halothane anesthesia
Authors: Iadecola C. , Zhang F. , Xu X.
Published: December 2017

We studied the effect of halothane anesthesia on the increases in cerebral blood flow (CBF) and arterial pressure (AP) elicited by electrical stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized (0.75-2% halothane), instrumented for continuous recording of AP, and ventilated. The FN was stimulated through stereotaxically implanted microelectrodes. In CBF experiments the elevations in AP resulting from FN stimulation were eliminated by spinal cord transection at C1. After cord transection AP was maintained by intravenous phenylephrine. CBF or cerebral glucose utilization (CGU) was measured by laser-Doppler flowmetry or the 2-deoxyglucose method, respectively. FN stimulation produced increases in CBF that were graded with the intensity (10-150 microA) or frequency (10-150 Hz) of stimulation. At 1% halothane, FN stimulation (100 microA; 75 Hz; n = 8) increased CBF by 123 +/- 16%. The elevations in CBF were attenuated by increasing levels of halothane anesthesia in a dose-dependent manner. At halothane concentrations of 1.5 and 2% the CBF response to FN stimulation (100 microA; 75 Hz) was reduced by 58 +/- 6 and 77 +/- 4%, respectively (p < 0.05 from 0.75% halothane; analysis of variance and Tukey's test). In contrast, the increases in CBF elicited by hypercapnia were not attenuated (P > 0.05 from 0.75% halothane). At 1% halothane, FN stimulation did not change CGU in neocortex (frontal cortex: unstimulated 48 +/- 6, mumol.100 g-1.min-1, FN stimulation: 47 +/- 11; P > 0.05; n = 5/group). In the group of rats in which the pressor response was studied (n = 7), halothane produced a dose-dependent attenuation of the elevations in AP. The degree of attenuation of the AP response was comparable to that of the CBF response (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Anoxia-tolerant hepatocytes: model system for study of reversible metabolic suppression
Authors: Buck L. T. , Land S. C. , Hochachka P. W.
Published: December 2017

Chrysemys picta bellii is well known for its ability to survive extended anoxic periods and has been widely used as a model system to study anoxic metabolism. Described here is a method for the isolation of anoxia-tolerant hepatocytes from this species. Freshly isolated hepatocytes were determined to be viable based on trypan blue exclusion, gluconeogenic capacity from [14C]lactate, responsiveness to epinephrine and glucagon, and maintenance of cellular adenylate concentrations. Under anoxic conditions for 10 h there was no significant increase in cell staining and no decrease in cellular ATP concentration. Furthermore, the addition of cyanide at the 5-h mark did not result in any significant differences in these parameters; however, iodoacetate added at this time caused trypan blue staining to increase and ATP concentrations to fall. The rate of glucose production from the cells was threefold greater under anoxic than normoxic conditions, underscoring the important role of the liver in supplying substrate during anoxia. From the rate of O2 consumption and rate of lactate production under anaerobic conditions, ATP turnover rates were calculated to be 68.4 +/- 7.2 and 6.5 +/- 0.43 mumol ATP.g-1.h-1, respectively; this corresponds to a 90% decrease in metabolic rate during anoxia. Within a cellular system such as this the more complex regulatory mechanisms involved in a large coordinated reduction in metabolism can be probed.
Rapid alterations of hypothalamic and hippocampal bombesin-like peptide levels with feeding status
Authors: Merali Z. , Kateb C. C.
Published: December 2017

It has been suggested that bombesin (BN)-like peptides may play a physiological role in the control of food intake. We studied the time course of changes in the levels of central BN-like peptides during a meal. Four groups of animals were used: rats that were food (but not water) deprived for 12-h period (preprandial group) and then given access to food for either 10 min (partially satiated group) or 35 min (postprandial group). The fourth group constituted nondeprived controls (ad libitum fed group). BN-like immunoreactivity (BLI) of the hypothalamus, hippocampus, and medulla was determined using a radioimmunoassay. Our data revealed that at the hypothalamus, the BLI content dropped significantly after food deprivation (preprandially), and returned to the ad libitum fed control levels after the meal (postprandially). At the hippocampus, food deprivation did not affect the BLI levels; however, food ingestion significantly elevated the BLI content within 35 min. The medullary BLI levels failed to alter in relation to the feeding status. The observed rapid alterations suggest that the hypothalamic response to food intake is satiety linked and hence lend support to the contention that BN-like peptides play a physiological role in the central regulation of ingestive behavior. The alterations noted at the hippocampus implicate physiological role of BN-like peptides in other meal-associated processes (such as memory).
Atrial natriuretic factor counteracts sodium-retaining actions of insulin in normal men
Authors: Miller J. A. , Abouchacra S. , Zinman B. , Skorecki K. L. , Logan A. G.
Published: December 2017

It has been hypothesized that hyperinsulinemia is causally related to hypertension by its effect on renal sodium transport. To examine the relationship between the sodium-retaining actions of insulin and atrial natriuretic factor (ANF), 16 healthy subjects were studied on three occasions, approximately 1 wk apart, using standard clearance techniques to evaluate responses during the acute administration of insulin, low-dose ANF, or both. In study 1, the euglycemic clamp was used to increase plasma insulin 10-fold to an average of 320 +/- 14 (SE) pM. This maneuver produced an immediate and persistent fall in sodium excretion from 0.315 +/- 0.02 to 0.207 +/- 0.02 mmol/min (P < 0.001) independent of change in renal hemodynamics, lithium clearance, and catecholamines. The decline in sodium excretion was associated with a marked increase in fractional distal sodium reabsorption. Systolic and diastolic pressure did not change significantly. In study 2, low-dose ANF (0.3 pmol.kg-1.min-1) designed to raise plasma levels to twice baseline was administered simultaneously in a repeat of study 1. This maneuver abolished insulin-mediated sodium reabsorption. In study 3, low-dose ANF infusion alone produced no changes in tubular handling of sodium. Our findings indicate that insulin at levels found in hyperinsulinemic states caused sodium retention and that physiological increases in plasma ANF concentration abolished the sodium-retaining action of insulin. Our findings suggest that if hypertension is causally related to hyperinsulinemia, mechanisms besides renal sodium retention are responsible for the hypertensive properties of insulin.
Antioxidant defenses in the tolerance of freezing and anoxia by garter snakes
Authors: Hermes-Lima M. , Storey K. B.
Published: December 2017

The garter snake Thamnophis sirtalis parietalis can readily tolerate several hours of freezing or anoxia exposure. Both stresses halt oxygen availability to tissues and to endure these stresses snakes must cope with potential oxidative stress arising as a result of the ischemic/anoxic condition followed by reperfusion of aerated blood during recovery. To determine whether antioxidant defenses are important for freezing and anoxia survival, we monitored the activities of antioxidant enzymes and the levels of glutathione (GSH and GSSG) during freezing (5 h at -2.5 degrees C) and anoxia (10 h under N2 gas at 5 degrees C) exposures in three organs (muscle, liver, and lung) of snakes. Freezing resulted in a significant rise in the activity of muscle and lung catalase (by 183 and 63%) and in muscle glutathione peroxidase (52%). Anoxia enhanced muscle and liver superoxide dismutase activities (by 59 and 118%) and also caused a 57% increase in muscle GSH levels. The increase in muscle GSH concentration in anoxia (from 0.45 to 0.71 mM) could also stimulate muscle glutathione peroxidase activity in vivo by 1.5-fold because of its low affinity for GSH (Km = 11 mM). The ratio of GSSG/GSH was not affected by experimental state in any tissue, suggesting that oxidative stress did not occur during the freezing or anoxic exposure. Rather, H2O2- and O2(-)-detoxification systems may be activated in preparation for possible oxygen free radical overgeneration during thawing or reoxygenation. Antioxidant defenses appear to be part of the adaptive machinery for reptilian tolerance of freezing and anoxia.
Asymmetrical transfer of inert hydrophilic solutes across rat placenta
Authors: Stulc J. , Stulcova B.
Published: December 2017

Transfer of [14C]mannitol, 51Cr-labeled EDTA, and [14C]-inulin from mother to fetus and from fetus to mother was measured in rats under pentobarbital anesthesia. The clearance of the three substances from the mother to fetus (Kmf) was 2.69 +/- 0.38, 1.93 +/- 0.73, and 0.47 +/- 0.14 microliter/min (means +/- SE), respectively, and the clearance from fetus to mother (Kfm) was 5.97, 6.66, and 4.95 microliters/min, respectively (the SE could not be estimated). Kfm appears to be consistently higher than Kmf by an almost constant value of approximately 4 microliters/min. To explain this a hypothesis was proposed according to which volume flow circulates across the placenta. Solute-free water is driven transcellularly across the placental barrier from the maternal to the fetal side by a difference of osmotic pressure created by active transport of some solutes (mainly Na+) to the fetus. Water together with all solutes dissolved returns from fetus to mother by filtration through wide extracellular channels in the placenta down a hydrostatic pressure gradient.
Effects of anesthesia on cardiac and renal sympathetic nerve activities and plasma catecholamines
Authors: Matsukawa K. , Ninomiya I. , Nishiura N.
Published: December 2017

The effects of pentobarbital and chloralose on cardiac sympathetic nerve activity (CSNA), renal sympathetic nerve activity (RSNA), arterial pressure (AP), and heart rate (HR) were examined using conscious cats. Arterial blood was sampled intermittently to measure plasma epinephrine. Pentobarbital (25-30 mg/kg iv) decreased CSNA, RSNA, AP, and HR. The reduction of CSNA (71 +/- 7%) was larger and lasted longer than that of RSNA (33 +/- 12%). Chloralose (40-50 mg/kg iv) decreased CSNA 66 +/- 9% and HR, increased RSNA 127 +/- 122%, and did not affect AP. The baroreflex relationship between AP and CSNA was examined by increasing AP to 145 mmHg and decreasing AP to 55 mmHg. Both pentobarbital and chloralose shifted the AP-CSNA relationship curve downward and blunted the slope of the curve, indicating that both drugs attenuate tonic and baroreflex cardiac sympathetic outflow. Pentobarbital and chloralose reduced plasma epinephrine, suggesting a decrease in adrenal sympathetic nerve activity. It is concluded that pentobarbital or chloralose affects differentially sympathetic outflows to different organs such as the heart, kidney, and adrenal gland.
Decreased potency of contraction to alpha-adrenoceptor stimulation in renal arteries from obese hypertensive dogs
Authors: Ratz P. H. , West D. B. , Granger J. P.
Published: December 2017

The contractile potencies of the alpha-adrenoceptor agonist phenylephrine (PhE) and two nonadrenergic vasoconstrictors, prostaglandin F2 alpha (PGF2 alpha) and endothelin, were evaluated in renal arterial muscle strips isolated from obese hypertensive (OH) dogs. Responses were compared with those obtained from renal arteries isolated from lean normotensive (LN) dogs. Identical dose-response curves were produced by PGF2 alpha in arteries from OH and LN dogs. This was also true for endothelin. However, the vasoconstrictor potency of PhE for arteries from OH dogs was approximately 2.5-fold less than that for arteries from LN dogs. This difference was not dependent on endothelial integrity. Although they were less potent to PhE, arteries from OH dogs did not produce weaker maximum contractile responses than arteries from LN dogs; responses produced by maximum K+ depolarization (S(o)) were approximately 2 x 10(5) N/m2, and responses to the maximally effective concentrations of PhE, PGF2 alpha, and endothelin were approximately 0.97-, 0.50-, and 0.87-fold S(o), respectively. In addition to the rightward shift in contractile potency to PhE, arteries from OH dogs precontracted with a maximum PhE concentration relaxed more to a high nitroglycerin concentration than did arteries from LN dogs. At a PhE concentration that produced equivalent maximum force responses, arteries from OH dogs had a lower rate of muscle shortening than did arteries from LN dogs, suggesting reduced cross-bridge activation in the arteries from OH dogs. These data suggest that alpha-adrenoceptor-induced activation was selectively downregulated in renal arteries from OH dogs.
Adaptations of plasma membrane glucose transport facilitate cryoprotectant distribution in freeze-tolerant frogs
Authors: King P. A. , Rosholt M. N. , Storey K. B.
Published: December 2017

Natural freeze tolerance in several anuran species involves the accumulation of high concentrations of glucose as a cryoprotectant in body fluids and tissues. The present study identifies an important new molecular mechanism supporting freeze tolerance, an adaptive increase in the capacity for facilitated transport of cryoprotectant across plasma membranes by increasing the numbers and/or activity of plasma membrane glucose transporters. Glucose transport by membranes isolated from liver and skeletal muscle was analyzed in two species, the freeze-tolerant wood frog Rana sylvatica and the freeze-intolerant leopard frog Rana pipiens. Membranes from both liver and muscle of R. sylvatica displayed much higher rates of carrier-mediated glucose transport, measured by a rapid filtration technique, compared with corresponding rates for R. pipiens membranes. For the liver Vmax values for glucose transport by membrane vesicles were 69 +/- 18 and 8.4 +/- 2.3 nmol.mg protein-1.s-1 at 10 degrees C for R. sylvatica and R. pipiens, respectively. This difference was due primarily to a greater number of glucose transporters in R. sylvatica liver membranes; the total number of transporter sites, determined by cytochalasin B binding, was 4.7-fold higher in the freeze-tolerant species. For muscle membranes, the Vmax for glucose transport was 4.9 +/- 1 and 0.6 +/- 0.16 nmol.mg-1 x s-1 at 22 degrees C for R. sylvatica and R. pipiens, respectively. However, in muscle there were no differences in the number of membrane transporters between species.(ABSTRACT TRUNCATED AT 250 WORDS)
Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones?
Authors: Satinoff E. , Li H. , Tcheng T. K. , Liu C. , McArthur A. J. , Medanic M. , Gillette M. U.
Published: December 2017

The basis of the decline in circadian rhythms with aging was addressed by comparing the patterns of three behavioral rhythms in young and old rats with the in vitro rhythm of neuronal activity in the suprachiasmatic nuclei (SCN), the primary circadian pacemaker. In some old rats, rhythms of body temperature, drinking, and activity retained significant 24-h periodicities in entraining light-dark cycles; in others, one or two of the rhythms became aperiodic. When these rats were 23-27.5 mo old they were killed, and single-unit firing rates in SCN brain slices were recorded continuously for 30 h. There was significant damping of mean peak neuronal firing rates in old rats compared with young. SCN neuronal activities were analyzed with reference to previous entrained behavioral rhythm patterns of individual rats as well. Neuronal activity from rats with prior aperiodic behavioral rhythms was erratic, as expected. Neuronal activity from rats that were still maintaining significant 24-h behavioral rhythmicity at the time they were killed was erratic in most cases but normally rhythmic in others. Thus there was no more congruence between the behavioral rhythms and the brain slice rhythms than there was among the behavioral rhythms alone. These results, the first to demonstrate aberrant SCN firing patterns and a decrease in amplitude in old rats, imply that aging could either disrupt coupling between SCN pacemaker cells or their output, or cause deterioration of the pacemaking properties of SCN cells.
Oral sensory stimulation in men: effects on insulin, C-peptide, and catecholamines
Authors: Teff K. L. , Levin B. E. , Engelman K.
Published: December 2017

To investigate the effect of oral sensory stimulation on cephalic phase insulin release (CPIR) and other compounds associated with glucose metabolism, a modified sham feed was used in which male subjects (n = 15) tasted, chewed, and then expectorated the food stimulus. Subjects remained fasted, sham fed, or ingested food on separate days over a 5-day period. After four baseline blood samples, poststimulus samples were taken every 2 min for 14 min and then every 15 min for 2.25 h. Increases in plasma insulin and C-peptide were found during the cephalic phase time period (0-10 min poststimulus) on the sham-fed and fed conditions when compared with fasted values. Glucose, norepinephrine, epinephrine, and free fatty acids were not affected by oral sensory stimulation or food ingestion during the cephalic phase period. The magnitude and profile of CPIR were similar after sham feeding and food ingestion. This study demonstrates that oral sensory stimulation can elicit CPIR in humans independently of changes in blood glucose.
Estimation of rate constants for serotonin uptake and compartmentation in normal human platelets
Authors: Launay G. , Costa J. L. , Da Prada M. , Launay J. M.
Published: December 2017

Biochemical and pharmacological experiments led to a model describing a thrombin-releasable (vesicular) compartment and two non-thrombin-releasable compartments for 5-hydroxytryptamine (5-HT, serotonin) in normal human platelets (J. L. Costa, K. L. Kirk, D. L. Murphy, and H. Stark. Br. J. Pharmacol. 72: 449-459, 1981). With tritiated 5-HT as substrate, the amounts of total and nonreleasable intraplatelet tritiated material were measured. Moreover, in the last set of experiments, the amounts of extraplatelet tritiated material and extraplatelet tritiated 5-HT were also measured. With these data, identification of the kinetic constants for movement between the various compartments was possible. A recent extension of the similarity transformation approach to nonlinear compartmental models was used to carry out the a priori identifiability analysis. Then numerical identification was performed by implementing and achieving efficient methods from optimal control theory. Under our experimental conditions, the main results are as follows: 1) the vesicular compartment corresponds to the platelet storage 5-HT compartment, 2) instead of pools I and II proposed previously, only a single nonreleasable thrombin-resistant pool could be detected, and 3) the optimized model computed to suit the first set of experiments fits homologous intraplatelet results obtained under similar experimental conditions in the last set of experiments and also fits one of the two supplementary extraplatelet investigations.
Enhancement of canine taste responses to umami substances by salts
Authors: Ugawa T. , Kurihara K.
Published: December 2017

The effects of salts on canine taste responses to umami substances were examined by recording the activity of the chorda tympani nerve. 1) The responses to monosodium glutamate (MSG), disodium 5'-guanylate (GMP), and that induced by the synergism between MSG and GMP were enhanced by the presence of various salts. 2) The effective salts were those carrying inorganic cations such as Na, K, and Mg, while CaCl2 had no enhancing effect. Salts carrying organic cations such as tris(hydroxymethyl)aminomethane (Tris), choline, N-methyl-D-glucamine, and 1,3-bis[tris(hydroxymethyl)-methylamino]propane also produced positive results. 3) The dependence of the umami responses on NaCl and MgCl2 concentrations showed a bell-shaped response curve with the maximal enhancing effect being seen at 100 mM NaCl and 3-10 mM MgCl2. 4) The degree of the enhancement depended not only on the species of the cation, but also on that of anion. For example, 100 mM NaCl showed a much larger enhancing effect than Na phosphate, Na2SO4, and Na4Fe(CN)6 at equimolar Na+. 5) The enhancing effects of salts on the responses to the umami substances could not be simply explained in terms of the permeability of cation and anion of salts. It was speculated that the binding of both cations and anions to the receptor membranes leads to changes in the interaction of the umami substances with the receptor proteins.
Increased capacity for circulatory fatty acid transport in a highly aerobic mammal
Authors: McClelland G. , Zwingelstein G. , Taylor C. R. , Weber J. M.
Published: December 2017

Plasma fatty acid (FA) and albumin concentrations, cardiac output, and hematocrit of dogs and goats [dog-to-goat ratio of maximal oxygen consumption (VO2max) = 2.2] were measured to determine rates of circulatory FA delivery during exercise. Our goals were 1) to characterize the mechanism(s) used by the endurance-adapted species (dog) to support higher rates of FA delivery to working muscles than the sedentary species (goat) and 2) to determine whether circulatory transport is scaled with VO2max. Lipid oxidation was 2.5 times higher in dogs than in goats. Dogs had higher cardiac outputs than goats, but this positive effect on their FA delivery was canceled by higher hematocrit. Dogs always had higher plasma FA concentrations than goats. In contrast, albumin was steady and identical in both species, showing that dogs transport FA at higher rates than goats only because they load more FA on their albumin. Average dog-to-goat ratios for FA delivery (1.5-2.0) were lower than would be expected if this rate were scaled with VO2max. In vitro experiments showed that dog albumin is designed for high rates of FA transport because it can bind 50% more FA than goat albumin. All endurance-adapted species may possess such "aerobic albumins" to supply more circulating FA to their working muscles than sedentary species.
Interleukin-1 beta causes the increase in anterior hypothalamic interleukin-6 during LPS-induced fever in rats
Authors: Klir J. J. , McClellan J. L. , Kluger M. J.
Published: December 2017

The purpose of this study was to determine, using push-pull perfusion, whether the central pyrogenic action of interleukin-6 (IL-6) during lipopolysaccharide (LPS)-induced fever in rats is induced by interleukin-1 beta (IL-1 beta) and to determine the source of the hypothalamic IL-6 (i.e., from the periphery or from the brain). Samples of cerebrospinal fluid were collected 60 min before and 60, 120, 180, and 240 min after the intraperitoneal injection of LPS or saline as a control. Immediately before the injection of LPS, anti-rat neutralizing IL-1 beta antibody (anti-IL-1 beta) or control immunoglobulin G antibody (IgG) was microinjected into the anterior hypothalamus (AH) of each rat. At the end of the last perfusion, blood was collected by cardiac puncture. Microinjection of anti-IL-1 beta into the AH caused a 58% reduction of LPS fever (measured by biotelemetry). AH microinjection of anti-IL-1 beta or IgG followed by intraperitoneal injection of saline did not result in significant change in core body temperature. AH injection of anti-IL-1 beta also resulted in a 97% reduction in AH IL-6 levels during LPS fever, with the average values of IL-6 for the four post-LPS time points being 113 +/- 50 U/ml for the rats injected with IgG and LPS and 3 +/- 2 U/ml for the rats injected with anti-IL-1 beta and LPS (P = 0.024).(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin secretion after stimulation of abdominal vagus in rabbit: role of A1 norepinephrine neurons
Authors: Gieroba Z. J. , Blessing W. W.
Published: December 2017

We determined whether electrical stimulation of the abdominal vagus nerve causes secretion of vasopressin in the rabbit and whether inhibition of neuronal function in the A1 region of the medulla oblongata impairs this secretion. In urethan-anesthetized rabbits, electrical stimulation of the abdominal vagus (5-min train of cathodal pulses, 0.5 ms duration, 20 Hz, 0.5-1 mA) increased plasma vasopressin from 37 +/- 8 to 133 +/- 19 pg/ml (P < 0.01, n = 11). Prior section of the cervical vagus completely prevented the increase seen with stimulation of the abdominal vagus. Injecting the inhibitory agent muscimol (1 nmol) 2 mm dorsal to the A1 area did not significantly reduce the vasopressin response to abdominal vagal stimulation. However, when muscimol was injected into the A1 area, the vagally mediated increase in plasma vasopressin was completely prevented. Our results show that stimulation of abdominal vagal afferents causes secretion of vasopressin in the rabbit via a central pathway that includes neurons in the A1 area.
Fasting alters basal and stimulated ion transport in piglet jejunum
Authors: Carey H. V. , Hayden U. L. , Tucker K. E.
Published: December 2017

Three-week-old piglets were used to study the effects of short-term fasting on jejunal ion transport. A 48-h fast significantly reduced mucosal weight, villus height, and crypt depth. Fasting increased basal short-circuit current (Isc), which reflects active ion transport, and total tissue conductance (Gt) of muscle-stripped jejunal sheets mounted in Ussing chambers. Increases in Isc evoked by carbachol, serotonin, histamine, prostaglandin E2, or Escherichia coli heat-stable enterotoxin were significantly greater in the fasted piglets. Isc responses to mucosal D-glucose were also enhanced by the fast. Under basal conditions, unidirectional and net fluxes of Na+ and Cl-, as well as serosal-to-mucosal inulin fluxes, were significantly increased in fasted piglets. In fed piglets, carbachol increased net Cl- secretion by stimulating serosal-to-mucosal Cl- flux; Gt was not affected. In fasted piglets, carbachol increased net Cl- secretion by inhibiting mucosal-to-serosal fluxes with no effect on serosal-to-mucosal fluxes. In addition, carbachol significantly inhibited mucosal-to-serosal Na+ fluxes and reduced Gt in this group. Thus a 48-h fast increased unidirectional and net ion fluxes in piglet jejunum and enhanced ion transport responses to secretory agonists. The mechanism by which carbachol stimulated net Cl- secretion was also altered by the fast. These results suggest that the absence of luminal nutrition changes the ion transport characteristics of the jejunal epithelium.
Endocrine changes associated with a rapidly developing sodium appetite in rats
Authors: Thunhorst R. L. , Morris M. , Johnson A. K.
Published: December 2017

Simultaneous administration of the diuretic furosemide (10 mg/kg) and a low dose of the angiotensin-converting enzyme (ACE) inhibitor captopril (5 mg/kg) results in short-latency thirst and sodium appetite (i.e., the rapid ingestion of water and NaCl solution). To elucidate potential mechanisms for mediating this behavior, changes in plasma levels of key hormones involved in fluid intake and balance were characterized in rats subjected to this treatment protocol. Rats treated jointly with furosemide and low-dose captopril had exaggerated increases in plasma renin activity and angiotensin I but equivalent increases in plasma aldosterone compared with rats treated with either agent alone. Treatment with furosemide plus low-dose captopril increased plasma vasopressin but not plasma oxytocin. The administration of a higher dose of captopril (100 mg/kg) with furosemide, a combination of drugs that does not stimulate fluid intake (29), further increased plasma renin activity and angiotensin I but prevented the rise in plasma vasopressin. The results support the hypothesis that thirst and salt appetite generated by this protocol depend on angiotensin II formed within brain circumventricular organs rather than the systemic circulation.
Frog glomerular vasotocin receptors resemble mammalian V1b receptors
Authors: Ammar A. , Rajerison R. M. , Roseau S. , Bloch-Faure M. , Butlen D.
Published: December 2017

Vasotocin receptors were investigated in glomeruli and nephron segments microdissected from collagenase-treated kidneys of Rana ridibunda, using [d(CH2)5Tyr(Me)2,Thr4,Orn8,125I-Tyr-NH2(9)]vasotocin (125I-OVTA) as a radioligand. Specific 125I-OVTA binding sites were found only in glomeruli and not in all tubule segments tested. Glomerular receptors exhibited the following stereospecificity for recognition of vasotocin analogues: Tyr-NH2(9)-LA-V1a > 125I-OVTA > arginine vasotocin (AVT) > or = [d(CH2)5Tyr-(Me)2]AVP > OVTA > or = [Phe2,Orn8]VT > oxytocin (OT) > or = [d(CH2)5-Sar7]AVP > desGly9[d(CH2)5Tyr(Et)2]VAVP > or = [d(CH2)5Tyr(Et)2]VAVP > AVP > [1-desamino-8-D-arginine]vasopressin (DDAVP) > [Thr4,Gly7]OT. In addition, vasotocin enhanced [3H]inositol phosphate production in sieved glomeruli labeled with myo-[3H]inositol; the rank order of structural vasotocin analogues for stimulation of phosphoinositidase C was [Phe2,Orn8]VT > AVT > OT > AVP > DDAVP, whereas [Thr4,Gly7]OT was almost inactive, and the rank order of antagonists for inhibition of hormone-induced enzyme activation was Tyr-NH2(9)-LA-V1a > [d(CH2)5Tyr(Me)2]AVP = OVTA > [d(CH2)5Sar7]AVP > [d(CH2)5Tyr(Et)2]VAVP > or = desGly9[d(CH2)5Tyr(Et)2]VAVP. Results indicate that the 125I-OVTA-labeled binding sites detected in frog glomeruli reveal the pharmacological properties of mammalian V1b-pituitary vasopressin receptors and might be physiological vasotocin receptors involved in phosphoinositidase C stimulation.
Intracerebroventricular insulin produces nonuniform regional increases in sympathetic nerve activity
Authors: Muntzel M. S. , Morgan D. A. , Mark A. L. , Johnson A. K.
Published: December 2017

Insulin has been shown to increase sympathetic nerve activity (SNA). Although it has been proposed that insulin acts within the central nervous system (CNS) to increase sympathetic neural outflow, there is little evidence for direct central neural sympathoexcitatory effects of insulin. To determine whether intracerebroventricular insulin elicits increases in peripheral SNA, we infused insulin (0.1 microU/min, low; 10 microU/min, medium; and 100 microU/min, high doses) or artificial cerebrospinal fluid (aCSF) into the third cerebral ventricle of chloralose-anesthetized Wistar rats while recording lumbar SNA. In separate animals, 10 microU/min of insulin were infused while recording adrenal SNA and renal SNA. Blood glucose and plasma insulin levels did not significantly change during intracerebroventricular infusion of insulin. Lumbar SNA, expressed as percentage of baseline, did not change in rats infused with aCSF (+ 13% +/- 8%) but increased significantly in rats infused with low (+ 72 +/- 17%), medium (+ 119 +/- 30%), and high (+ 113 +/- 25%) doses of insulin (P < 0.05). Intracerebroventricular insulin failed to significantly increase adrenal SNA or renal SNA. Blood pressure and heart rate did not change during insulin infusion. The results indicate that administration of insulin into the third cerebral ventricle produces regionally nonuniform increases in sympathetic neural outflow in the absence of changes in blood glucose or plasma insulin.
Functional assessment of the 5-HT 1A-, 1B-, 2A/2C-, and 3-receptor subtypes on food intake and metabolic rate in rats
Authors: Bovetto S. , Richard D.
Published: December 2017

The 5-hydroxytryptamine (5-HT) agonists (+/-)-8-hydroxydipropylaminotetralin hydrobromide (8-OH-DPAT), RU-24969, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), and 1-phenylbiguanide were administered to male Wistar rats to assess the respective involvement of the 5-HT 1A-, 1B-, 2A/2C-, and 3-receptor subtypes in the control of food intake and metabolic rate (VO2). Four series of experiments were carried out, each series addressing the effects of four doses (including saline or dose 0) of each of the agonists selected. The drugs were intraperitoneally injected in spontaneously fed animals. Injections were performed during the first 15 min of either the diurnal or the nocturnal phases of the light-dark daily cycle. Food intake and VO2 measurements were carried out over the 12-h periods ensuing after the agonist injections. The two highest doses of the 5-HT1A-receptor agonist 8-OH-DPAT led to a quickly appearing but transient elevation of diurnal VO2. During the night, VO2 was higher when the rats were treated with 8-OH-DPAT than when they were treated with saline. There was no significant effect of 8-OH-DPAT on either diurnal or noctural food intake. The highest dose of RU-24969 induced a significant increase in diurnal VO2, whereas all doses of RU-24969 blunted the nocturnal rise in metabolic rate characteristically observed in rats kept under a daily light-dark cycle. Importantly, RU-24969 induced marked diurnal and nocturnal hypophagia.(ABSTRACT TRUNCATED AT 250 WORDS)