bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of carbonic anhydrases in type I muscle fibers influences contractility
Authors: Côté C. , Tremblay D. , Riverin H. , Frémont P. , Rogers P. A.
Published: April 2011

We tested the effects of inhibiting the carbonic anhydrase activity of rat soleus and extensor digitorum longus muscles on the isometric contractile properties and the resistance to fatigue. SOL and EDL muscles from female rats were incubated in vitro in the presence of methazolamide, a specific inhibitor of carbonic anhydrase, before determining their contractile properties. Methazolamide had no effects on the contractile properties of the soleus muscle (10−5 or 10−3 M) and extensor digitorum longus (10−3 M), except for the half-relaxation time of the soleus muscle which increased significantly. Values for half-relaxation time were significantly increased with both concentrations of the inhibitor. Muscles were then submitted to a fatigue protocol lasting 30 min. During the fatigue test, no significant difference was observed between control and 10−5 M methazolamide soleus muscles. In presence of 10−3 M methazolamide however, the soleus muscle showed a significantly increased resistance to fatigue compared with control preparations. No significant effect was observed with the extensor digitorum longus muscle exposed to 10−3 M methazolamide. Results are discussed in terms of the presence of two different isoforms of carbonic anhydrase that may be associated with calcium uptake and energy metabolic processes, respectively.Key words: carbonic anhydrase, skeletal muscle, contraction, fatigue, soleus muscle.
Effect of acute, multiple-dose ethanol on maternal and fetal blood gases and acid–base balance in the near-term pregnant ewe
Authors: Smith Graeme N. , Brien James F. , Carmichael Lesley , Clarke David W. , Patrick John
Published: April 2011

The effect of ethanol on maternal and fetal blood gases and acid–base balance was determined in six conscious instrumented near-term pregnant ewes for maternal intravenous infusion of 3 g ethanol/kg total body weight administered as six doses of 0.5 g ethanol/kg total body weight over 8 h. Maternal and fetal blood ethanol concentrations, determined in two animals, were maximal at 8 h (3.74 and 3.82 mg/mL, respectively) and were virtually identical during the 24-h study. Maternal and fetal blood gases and acid-base balance were not significantly altered during and after ethanol administration compared with pre-infusion values. The data demonstrate that, during near-term ovine pregnancy, the equivalent of a binge-type drinking episode does not produce fetal hypoxia or acidosis. Furthermore, these data do not support the postulated involvement of ethanol-induced fetal hypoxia in the mechanism of ethanol teratogenesis.Key words: ethanol, blood gases, pregnancy, fetus, maternal.
Fish oil prevents effect of high cholesterol diet on active intestinal transport of galactose
Authors: Thomson A. B. R. , Keelan M. , Garg M. L. , Clandinin M. T.
Published: April 2011

We tested the hypothesis that diets containing fish oils prevent the effects of a high cholesterol diet on the morphology and nutrient uptake of the intestine. Isocaloric semisynthetic diets were supplemented with beef tallow or fish oil containing low or high amounts of cholesterol and were fed to growing female Wistar rats for 14 days, after which the in vitro jejunal and ileal uptake of glucose, galactose, long-chain fatty acids, and cholesterol was determined. Feeding cholesterol with beef tallow was associated with a 12% decrease in the jejunal mucosal surface area. Feeding fish oil decreased jejunal mucosal surface area by 24%, as compared with the beef tallow diet, but the reduction was increased to 42% when fish oil and cholesterol were fed together. Ileal surface area was unaffected by varying the major source of dietary lipid, or by adding cholesterol. Despite the effect of fish oil on the mucosal surface area, the jejunal and ileal uptake of saturated as well as unsaturated long-chain fatty acids and cholesterol was similar in the four diet groups. Cholesterol supplementation enhanced the jejunal uptake of high concentrations of galactose only when fed with beef tallow, i.e., feeding fish oil prevented the enhancing effect of cholesterol on galactose uptake observed when beef tallow was fed. Thus, (i) a fish oil diet prevents the enhancing effect of cholesterol on jejunal active transport of galactose, an effect not explained by the reduction in jejunal mucosal surface area observed with the fish oil diet; (ii) these dietary manipulations result in a clear dissociation of the morphological from the transport adaptation of the intestine; and (iii) substitution of fish oil for beef tallow as the major source of lipid in the diet prevents the influence of cholesterol on the active intestinal transport of galactose.Key words: adaptation, dietary cholesterol, galactose, glucose, long-chain fatty acids, permeation, fish oil.
Effects of GTP analogs and dithiothreitol on the binding properties of the vascular vasoactive intestinal peptide receptor
Authors: Huang Minta , Rorstad O. P.
Published: April 2011

Previous studies have demonstrated a specific vascular receptor for the neurotransmitter peptide, vasoactive intestinal peptide (VIP), and have suggested that the receptor is positively coupled to vascular adenylate cyclase. The present study addressed the questions whether the vascular VIP receptor is subject to regulation by guanine nucleotides and whether a disulfide reducing agent, dithiothreitol, would perturb the binding function of the vascular VIP receptor. Guanosine triphosphate (GTP) and its non-hydrolyzable analogs, guanylyl imidodiphosphate (Gpp(NH)p) and guanosine-5′-O-(3-thiotriphosphate) (GTP-γ-S), increased the rate of dissociation of radiolabeled VIP from arterial receptors in a concentration-dependent manner. GTP-γ-S increased the equilibrium dissociation constant (KD) of the high affinity vascular VIP binding site, a result consistent with decreased high affinity binding of VIP induced by GTP-γ-S. These results are consistent with a regulatory role for guanine nucleotides in the function of the vascular VIP receptor. The disulfide reducing agent, dithiothreitol, caused a decrease in specific binding of radiolabeled VIP. Upon Scatchard analysis the effect of dithiothreitol was characterized by an increase in the KD and a decrease in the maximum number of binding sites (Bmax) of the high affinity binding site. These results suggest that disulfide bonds are important for ligand binding to vascular VIP receptors. The sulfhydryl alkylating agents, N-ethylmaleimide and iodoacetamide, had minimal effects on radioligand binding.Key words: vasoactive intestinal peptide receptor, blood vessel, GTP, receptor regulation.
Mechanism of action of luteinizing hormone-releasing hormone in rat ovarian cells
Authors: Leung Peter C. K. , Wang Jian , Baimbridge Kenneth G.
Published: April 2011

The initial step in the signal transduction of luteinizing hormone-releasing hormone (LHRH) in rat ovarian cells is the hydrolysis of membrane polyphosphoinositides into inositol phosphates and 1,2-diacylglycerol. The former compounds, especially inositol 1,4,5-triphosphate, are known to cause the release of calcium from intracellular stores, while diacylglycerol is a potent activator of protein kinase C. LHRH causes a rapid and transient increase in intracellular concentrations of free calcium ions, by approximately 4.5-fold, in the majority of granulosa cells as assessed by fura-2 microspectrofluorimetry. Like LHRH, a calcium ionophore (A23187) and activators of protein kinase C attenuate the steroidogenic response of the cells to follicle-stimulating hormone, but enhance the formation of gonadotropin-induced prostaglandin formation. These results support the concept that stimulation of polyphosphoinositide hydrolysis is intimitely involved in the direct action of LHRH at the level of the ovary.Key words: signal transduction, calcium, protein kinase C, ovary, steroid hormones.
Vascular neuroeffector mechanisms in hypertension
Authors: Cheung D. W.
Published: April 2011

Recent studies of the peripheral sympathetic nervous system indicate the presence of other vasoactive transmitters in addition to noradrenaline. There is now evidence suggesting ATP to be a co-transmitter of noradrenaline mediating the excitatory junction potential and the phentolamine-resistant component of the vasopressor response. In hypertension, changes in the neural regulation at both pre- and post-synaptic levels have been observed. In the spontaneously hypertensive rat (SHR), abnormal feedback regulation through presynaptic adrenoceptors and increases in release and uptake by the perivascular nerves are well characterized. Whether similar changes in the ATP release mechanism occur in the SHR and other forms of hypertension remain to be determined. A more important role for ATP in the neural regulation of the SHR tail artery has been proposed. In future studies, the possible contribution of co-transmitters to the responses should be taken into consideration.Key words: hypertension, noradrenaline, ATP, sympathetic nervous system.
Cocaine: Pharmacokinetics and biotransformation in man
Authors: Inaba T.
Published: April 2011

Pharmacokinetic studies of cocaine have been carried out only in the last decade, although its local anesthetic action and addictive properties have been known for almost 100 years. Elimination half-lives of cocaine in man estimated from serial plasma concentration are relatively short and range from 0.5 to 1.1 h after i.v. and 0.9–1.5 h after administration by the nasal or oral route. The bioavailability after nasal inhalation is about 60%. The bicyclic structure of cocaine is characterized by functional groups including N-methyl, carboxyl methyl ester, and benzoyl ester, which are susceptible to biotransformation. Hydrolysis of the benzoyl group to ecgonine methyl ester is catalyzed by plasma cholinesterase and is thus under monogenic control. The hydrolytic cleavage of the other ester group, methyl ester, to benzoyl ecgonine occurs spontaneously at body temperature. In contrast, N-demethylation of cocaine mediated by microsomal cytochrome P-450 produces norcocaine and this metabolite was shown to be pharmacologically active, the action being similar to cocaine.Key words: cocaine, hydrolysis, plasma cholinesterase, cytochrome P-450.
Effects of acetylcholine, propranolol, and verapamil on sinus node refractoriness of the rabbit
Authors: Kerr Charles R.
Published: April 2011

At a critical premature interval, atrial premature beats encounter sinus node refractoriness and are blocked on entering and fail to reset the sinus node, resulting in interpolation of the premature beat. The transition from reset to interpolated response has been used to define the effective refractory period of the sinus node (SNERP). In an in vitro preparation of rabbit sinus node, we evaluated the effects of acetylcholine, propranolol, and verapamil on SNERP. Results obtained in the control state were compared with those obtained during superfusion with drugs, all of which prolonged refractoriness: acetylcholine from 233 ± 41 (SD) to 325 ± 88 ms; propranolol from 215 ± 60 to 241 ± 67 ms; and verapamil from 192 ± 69 to 254 ± 79 ms (p < 0.005 with all drugs). The site of block of premature beats was mapped between sinus node and crista terminalis with an intracellular microelectrode. All three drugs resulted in block of premature beats at sites farther from the primary pacemaker site. Thus, acetylcholine, propranolol, and verapamil prolong sinus node refractoriness.Key words: acetylcholine, propranolol, verapamil, sinus node, sinus node refractoriness.
Effects of long-term exposure to hydrostatic pressure per se (101 ATA) on eel metabolism
Authors: Simon B. , Sebert P. , Barthelemy L.
Published: April 2011

Oxygen consumption, [Formula: see text], has been measured in yellow freshwater eels (Anguilla anguilla L.) exposed in normoxic conditions for 31 days at a hydrostatic pressure of 101 ATA (atmosphere absolute; 1 ATA = 0.1 MPa) using a high pressure water circulation system. The results (series I) show that from a maximal value observed at the end of compression, [Formula: see text] decreases exponentially with time [Formula: see text] then reaches a steady state [Formula: see text] at a lower level than observed at 1 ATA before compression [Formula: see text]. These observations are in agreement with the hypothesis that shallow water fish are able to adapt to pressure; the possible mechanisms of this adaptation are discussed. Results from a second experimental series show that fish previously submitted to pressure for 1 month (then decompressed to 1 ATA) adjust faster to a new pressure exposure (4 days later) than fish that have never experienced pressure exposure. This observation suggests that the mechanisms triggered by long-term pressure exposure could persist, at least in part, for several days after decompression to atmospheric pressure.Key words: eel, metabolism, hydrostatic pressure, adaptation.
Effect of plasma from hypertensive patients on contractile response of vascular smooth muscle from normotensive rat
Authors: Pillai G. , Sutter M. C.
Published: April 2011

This study examines whether incubation with plasma from essential hypertensive patients increases the contractile activity of vascular smooth muscle from rats in response to noradrenaline (NA) and potassium (K+). Plasma samples were obtained from age- and sex-matched essential hypertensive patients and normotensive people. Vascular strips were prepared from aorta and portal veins of normotensive rats and placed in physiological solution in muscle baths for measurement of mechanical response. Aortic strips exposed to hypertensive plasma showed increased responsiveness to NA compared with normotensive plasma, but K+ caused an opposite effect. Portal vein exposed to normotensive or hypertensive plasma did not produce any response to NA, but the responsiveness produced in the presence of normotensive plasma to K+ was higher than that of hypertensive plasma. Portal vein exposed to normotensive plasma or hypertensive plasma showed a dose-dependent increase in the spontaneous activity up to 50% concentration of the plasma samples, but further increase in the concentration of plasma inhibited the spontaneous activity. Spontaneous activity at any given concentration of hypertensive plasma was significantly higher than that of normotensive plasma. The spontaneous activity in the presence of heated or unheated normotensive plasma or unheated normotensive serum was not significantly different from each other. These results indicate that the plasma factor from hypertensive patients, which alters the reactivity of vascular smooth muscle from normotensive rat, is present in the serum fraction and is not heat sensitive.Key words: hypertension, plasma, contractile response, circulating factor, spontaneous activity.
Characterization of a calcium-activated potassium channel in human fibroblasts
Authors: Stockbridge Lisa L. , French Andrew S.
Published: April 2011

The cell-attached and inside-out patch clamp techniques were used to record single-channel currents from human epidermal fibroblasts. A large-conductance channel (320 pS in symmetric 140 mM KCl) with high potassium selectivity was observed in many patches, particularly those located at the borders of the cells. The channel exhibited both voltage and calcium sensitivity and, therefore, was regarded as a variety of the large-conductance calcium-activated potassium channels reported in many preparations. Probability density functions, fitted to histograms of open and closed time durations at 35 °C, usually displayed a minimum of one open state and two closed states. However, kinetic analysis by the fractal method suggested more complicated behavior, particularly for the closed condition. It was not uncommon to observe several channels in one patch. This was distinguishable from the presence of subconductances, which were also observed. Although this channel could have many roles, it seems likely to mediate the calcium-activated conductance that underlies the hyperpolarizing response of fibroblasts to mechanical, electrical, or chemical stimuli.Key words: patch clamp, ion channel, fibroblast, subconductance.
Effect of exogenous insulin on plasma free carnitine levels during exercise in normal man
Authors: Broderick Tom L. , Poirier Paul , Tremblay Angelo , Catellier Claude , Nadeau André
Published: April 2011

Preliminary data from our laboratory have shown that the decrease in plasma free carnitine levels normally found during prolonged exercise is blunted in type 1 diabetic man. This study was designed to test the hypothesis that this might be due to the sustained peripheral hyperinsulinemia seen during exercise in diabetics treated by subcutaneous insulin. Ten male subjects underwent 90 min of cycle ergometry at 60% of their maximal oxygen uptake capacity on two occasions, one with and the other without a constant 0.13 mU∙kg−1∙min−1 i.v. insulin infusion. Blood samples were taken at rest, during exercise, and after exercise for measurement of plasma glucose, insulin, C-peptide, free fatty acids, and carnitine. Plasma glucose dropped significantly (p < 0.01) from basal during both infusions, but values at 30, 45, and 60 min of exercise were lower (p < 0.05) during insulin infusion compared with the saline infusion. Exercise produced a significant (p < 0.01) fall in plasma insulin in both infusions. However, from 30 to 90 min of exercise, the plateau insulin level was higher during the insulin infusion compared with the saline infusion (91.4 ± 3.0 vs. 32.9 ± 3.0 pmol/L; p < 0.001). Plasma C-peptide decreased significantly (p < 0.01) during exercise and recovery in both infusions, but values between infusions were not significantly different. Plasma free fatty acids increased significantly (p < 0.01) at 90 min of exercise during the saline infusion, while during the insulin infusion this was noted during recovery only. Free fatty acid values at 75 (p < 0.05) and 90 min (p < 0.01) of exercise, and during recovery (p < 0.01), were lower during the insulin infusion than during the saline infusion. Plasma free carnitine declined (p < 0.01) during exercise and recovery. However, at 60 min of exercise and at 30 min of recovery, free carnitine levels were significantly (p < 0.05) lower during the saline infusion compared with the insulin infusion. The decrement in surface area below baseline in free carnitine was greater during the saline infusion than in the insulin infusion (−298 ± 52 vs. −133 ± 29 μmol∙L−1∙min−1; p < 0.01). Esterified carnitine increased (p < 0.01) similarly during both infusions. These data indicate that the fall in plasma free carnitine during exercise can be reduced by an exogenous insulin infusion in normal man. Indirectly, this suggests that the absence of a decline in plasma free carnitine during exercise in diabetics can be explained by their high insulin levels.Key words: insulin, free carnitine, free fatty acids, acute exercise.
The relationship between post-tetanic potentiation of motor units and myosin isoforms in mouse soleus muscle
Authors: Parry D. J. , DiCori S.
Published: April 2011

Post-tetanic potentiation was measured in motor units, isolated functionally by ventral root splitting, of soleus and extensor digitorum longus muscles of mouse. All motor units from the extensor digitorum longus had times to peak twitch tension less than 13 ms; there was a linear relationship between time to peak tension and post-tetanic potentiation, with the faster units exhibiting greater potentiation. When soleus motor units were similarly analyzed, it appeared that there may be two distinct populations of units. Those units with times to peak tension less than 13 ms were virtually indistinguishable from those of extensor digitorum longus. On the other hand, the slope of the relationship between post-tetanic potentiation and time to peak tension was significantly lower for soleus units with times to peak tension of 13 ms or more. Approximately three-quarters of the soleus units were of the latter slow type, whereas only one-half of the muscle fibres could be classified as type I by means of immunohistochemistry, suggesting that the myosin heavy chain may not be the major determinant of post-tetanic potentiation. Single, chemically skinned fibres of soleus were analyzed for myosin heavy and light chain components by polyacrylamide gel electrophoresis. All fibres with type I heavy chain contained only the two slow light chains. On the other hand, almost all of the fibres with type IIA myosin heavy chain contained both fast and slow light chains. It is suggested that the discrepancy between the proportions of physiologically "fast" motor units and histochemical type IIA fibres may be the consequence of variable amounts of slow light chain associated with the fast IIA myosin heavy chain.Key words: post-tetanic potentiation, motor units, myosin isoforms, fibre types, immunohistochemistry.
The disulfide bonded ring of iso-rANP, unlike that of rANP, has potent cardiovascular activity
Authors: Jennings D. B. , Flynn T. G.
Published: April 2011

Iso-atrial natriuretic peptide (iso-rANP), a 45 amino acid peptide with a disulfide bond between residues 23 and 39, is a newly discovered second atrial hormone with considerable homology with rat atrial natriuretic peptide (rANP). We have reported that iso-rANP(1–45) has effects similar to rANP in anesthetized rats in causing hypotension, a decrease in heart rate, and an increase in urine flow and electrolyte excretion. In the present experiments, we found that, unlike the ring peptide of rANP (rANP(105–121)), bolus injections of the ring peptide of iso-rANP (iso-rANP(23–39)) had considerable effects on the circulation but only small effects on the kidney, compared with iso-rANP(1–45). However, the effects of iso-rANP(23–39) in causing hypotension and decreasing heart rate were transient compared with those of iso-rANP(1–45). When we substituted a glycine for arginine into the ring portion of iso-rANP at position 36, so that there were only three amino acids different from the ring of rANP, biological activity of iso-rANP(23–39) was retained. In our bioassay system, all of the circulatory effects and most of the renal effects of rANP are mediated via vagal sensory afferents. We found that the effects of the ring peptide of iso-rANP on the circulation and the kidney were unchanged following vagotomy. The results indicate that iso-rANP(23–39) mediates at least some biological effects by membrane receptor mechanisms different from those of rANP and that the ring portion of iso-rANP probably contributes to nonvagally mediated responses of iso-rANP(1–45).Key words: iso-atrial natriuretic peptide, structure–activity, receptor mechanisms, vagal chemoafferents.
A comparison of the size of fenestrations in the internal elastic lamina of young and old porcine aortas as seen with the scanning electron microscope
Authors: Dunmore P. Joy , Song S. H. , Roach Margot R.
Published: April 2011

The size of the fenestrations (windows) in the internal elastic lamina (IEL) of arteries may be important in the functioning of the blood vessel wall. The fenestrations are filled with collagen, muscle, and (or) ground substance, which must be removed to make the fenestration visible with the scanning electron microscope. All of the nonelastic components are removed with a hot alkali solution. Our experiments were designed to compare the fenestration size in the IEL of the thoracic aorta of young (6–8 weeks) and old (6–9 months) pigs. A protocol for digestion of young pig tissue was developed and showed that fresh young aortas should be digested in 0.1 M NaOH at 75 °C for 2 h and fixed tissue should be digested for 5 h. The average area of the fenestrations for young pig thoracic aortas digested for 2 h was 1.8 ± 0.29 (SE) μm2 and for the old pig aortas digested for 2 h was 1.7 ± 0.11 (SE) μm2. These values were not significantly different (p > 0.05), but the IEL from young pigs appeared rougher than the previously reported smooth IEL of the adult pigs.Key words: elastin, fixation, digestion, fenestration, scanning electron microscope.
Brain lactic acidosis and synaptic function
Authors: Walz Wolfgang , Harold Diane E.
Published: April 2011

Measurements of the presynaptic fiber volley (PSFV), the population excitatory postsynaptic potential (EPSP), and the extracellular pH in the dendritic CA1 layer of rat hippocampal slices were used to evaluate the effects of lactacidosis on central synaptic transmission. Replacement of NaCl with sodium lactate (up to 30 mM) was found not to affect the PSFV; however, the EPSP was reversibly suppressed. Sodium citrate, with added CaCl2 to adjust for Ca2+ chelation, had the same effect as sodium lactate. Addition of lactic acid influenced the PSFV only when, at a concentration of 30 mM, the extracellular pH dropped to 6.6 or lower. With lactic acid concentrations of up to 20 mM, which produced pH levels of 6.8 in the slice, effects on the EPSP were reversible. However, 30 mM lactic acid suppressed both the PSFV and EPSP irreversibly. These results show that synaptic transmission is much more susceptible to lactacidosis than presynaptic axonal transmission. They also show that high levels of lactate, albeit causing suppression of synaptic transmission, do not cause irreversible damage. However, acidosis associated with lactic acid release may damage synaptic transmission irreversibly.Key words: acidosis, hippocampal slice, ischemia, lactate, lactic acid, neuronal transmission, synapse.
Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin
Authors: Thornhill J. A. , Pittman Q. J.
Published: April 2011

Experiments were conducted (i) to determine the hemodynamic (blood pressure and heart rate) responses of conscious rats following intrathecal (IT) administration of endogenous prodynorphin-derived opioids into the lower thoracic space, (ii) to identify the receptors involved in mediating their cardiovascular responses, and (iii) to reveal any possible hemodynamic interactions with the neuropeptide arginine vasopressin. Male Sprague–Dawley rats were surgically prepared with femoral arterial and venous catheters as well as a spinal catheter (into lower thoracic region, T9–T12). After recovery, hemodynamic responses were observed in conscious rats for 5 – 10 min after IT injections of artificial cerebrospinal fluid (CSF) solution, prodynorphin-derived opioids (dynorphin A, dynorphin B, dynorphin A (1 – 13), dynorphin A (1 – 10), α- and β-neoendorphin, leucine enkephalin (LE), methionine enkephalin (ME), arginine vasopressin (AVP), or norepinephrine (NE)). IT injections of AVP (10 or 20 pmol), dynorphin A (1 – 13), or dynorphin A (10 – 20 nmol) caused pressor effects associated with a prolonged and significant bradycardia. Equimolar (20 nmol) concentrations of LE, ME, α- and β-neoendorphin, and dynorphin A (1 – 10) caused no significant blood pressure or heart rate changes. Combined IT injections of dynorphin A (1 – 13) and AVP caused apparent additive pressor effects when compared with the same dose of either peptide given alone. IT infusion of the specific AVP–V1 antagonist d(CH2)5Tyr(Me)AVP before subsequent IT AVP, dynorphin A (1 – 13), or NE administration inhibited only the subsequent pressor responses to AVP. The x-opioid antagonist (Mr2266) infused IT blocked the pressor actions of subsequent dynorphin A administration and not AVP or NE. These results indicate that dynorphin A and dynorphin A (1 – 13), in the doses used, given IT to conscious rats evoked pressor and bradycardic responses. The pressor actions of dynorphin A appear to be mediated by spinal x-opioid receptors and are independent of interaction with spinal AVP–V1 receptors.Key words: prodynorphin-derived peptides, arginine vasopressin, intrathecal administration, hemodynamic effects, specific receptor-mediated responses.
β-Lactoglobulin enhances the uptake of free palmitate by hepatocyte monolayers: the relative importance of diffusion and facilitated dissociation
Authors: Burczynski F. J. , Moran J. B. , Cai Z.-S. , Forker E. L.
Published: April 2011

We compared the uptake of bound palmitate by rat hepatocytes to its uptake by polyethylene using β-lactoglobulin (BLG) as the binding protein. The experiments were designed to supply a direct measure of the protein-dependent change in the diffusive conductance of extracellular fluid without determining the diffusion coefficients for free and bound fatty acid or the off-rate constant for protein binding. Rate-limiting dissociation in the stirred phase of extracellular fluid was excluded. The results obtained with BLG are strikingly similar to those previously obtained with albumin and provide additional circumstantial evidence that when the free fraction is small, palmitate uptake is partially driven by the concentration of bound fatty acid. Because this phenomenon is not specific for the binding protein, it may reflect direct exchange of ligand between the binding protein in extracellular fluid and the putative transport protein in the hepatocyte plasma membrane.Key words: codiffusion, stagnant layer, protein binding.
The origin of the vomiting response: a neuroanatomical hypothesis
Authors: Lawes L N. C.
Published: April 2011

The connections of area postrema include a set of nuclei with a common topographical location immediately deep to the ependyma or pia mater. These nuclei are all within two principal synapses of the area postrema and can be reached by more than one route from it. There is direct evidence that, like the area postrema, a number of these nuclei participate in vomiting. It is suggested that the paraventricular system may act as a distributed pattern generator for the several processes known to be integrated in the emetic response. It is also suggested that the other functions of the paraventricular nuclei, mainly homeostatic in mammals, have all evolved from a prototypical behaviour pattern of escape from, and subsequent avoidance of, noxious stimuli. Thus, through this system of nuclei, blood pressure, respiration, gastrointestinal motility and secretion, fluid and electrolyte balance, and the ingestion of food may all be influenced by noxious situations.Key words: vomiting, central autonomic pathways, homeostasis, escape, osmoregulation.
Regulatory peptides and the onset of nausea and vomiting
Authors: Kucharczyk John , Harding R. K.
Published: April 2011

There is no direct evidence that peptide hormones mediate vomiting observed during various cardiovascular, cerebrovascular, visceral, or neurological disorders. On the other hand, recent studies in animal models have demonstrated that several endogenous vasoactive neuropeptides can induce short-latency emesis following systemic or intracranial injections. This article reviews experimental data on peptide-induced emesis.Key words: emesis, neuropeptides, area postrema, angiotensin II, vasopressin.
Motion sickness: a synthesis and evaluation of the sensory conflict theory
Authors: Oman Charles M.
Published: April 2011

"Motion sickness" is the general term describing a group of common nausea syndromes originally attributed to motion-induced cerebral ischemia, stimulation of abdominal organ afferents, or overstimulation of the vestibular organs of the inner ear. Seasickness, car sickness, and airsickness are commonly experienced examples. However, the identification of other variants such as spectacle sickness and flight simulator sickness in which the physical motion of the head and body is normal or even absent has led to a succession of "sensory conflict" theories that offer a more comprehensive etiologic perspective. Implicit in the conflict theory is the hypothesis that neural and (or) humoral signals originate in regions of the brain subserving spatial orientation, and that these signals somehow traverse to other centers mediating sickness symptoms. Unfortunately, our present understanding of the neurophysiological basis of motion sickness is incomplete. No sensory conflict neuron or process has yet been physiologically identified. This paper reviews the types of stimuli that cause sickness and synthesizes a mathematical statement of the sensory conflict hypothesis based on observer theory from control engineering. A revised mathematical model is presented that describes the dynamic coupling between the putative conflict signals and nausea magnitude estimates. Based on the model, what properties would a conflict neuron be expected to have?Key words: motion sickness, nausea, vestibular, vision, mathematical models.
The possible involvement of calcium in renal proximal tubular reabsorptive defect in the rat after release of ureteral obstruction
Authors: Chatsudthipong V. , Sophasan S. , Jariyawat S.
Published: April 2011

The temporal relationship between changes in cytosolic free calcium and proximal tubular function was examined in rats following 24 h of unilateral and bilateral ureteral obstruction. Immediately after release of unilateral ureteral obstruction, proximal tubular functions were found to be normal. Cytosolic free calcium in isolated proximal tubules of the ureteral obstructed and contralateral kidneys were 160 ± 8 and 172 ± 15 nM, respectively. On the 7th day after release, cytosolic free calcium was not different from the sham control value (135 ± 6 vs. 149 ± 7 nM). In contrast, immediately after release of bilateral ureteral obstruction, cytosolic free calcium was increased significantly to 219 ± 6 from 139 ± 9 nM in sham-operated controls. Subsequent declines in cytosolic free calcium to 196 ± 15 and 148 ± 7 nM were observed at 3 and 7 days after release of bilateral ureteral obstruction, respectively. Over this period, renal tubular functions gradually returned to normal. Changes in cytosolic free calcium correlate well with the reported improvement in renal tubular function after release of bilateral ureteral obstruction. Therefore, one possible mechanism for the impairment of tubular function observed in bilateral ureteral obstruction may be an increase in cytosolic free calcium.Key words: ureteral obstruction, cytosolic free calcium, renal proximal tubule, rat.
Heptaminol-chlorhydrate agit sur un épithélium transporteur
Authors: Fontas Bernard , Mambrini Jean
Published: April 2011

[Journal translation]Electrophysiological and transport effects induced by heptaminol hydrochloride were studied in frog epithelium. This tissue, which can easily be maintained in vitro, is a valuable model for studying sodium active transport with hormone-dependent characteristics that reproduce mammalian nephron behavior (notably in areas with tight gap junctions). The two following techniques were used: the Ussing short-circuit current method and the swept-frequency impedance measurement method. Our findings indicate the following. (i) Heptaminol hydrochloride significantly increases the short-circuit current and transepithelial polarization. (ii) This effect develops progressively as the molecule is introduced on the serous side (3Na+/2K+ active countertransport sites). Time to maximum development is approximately 20 min and the electrophysiological effect lasts from 60 to 90 min. (iii) The mean equivalent cationic current rise is larger in sulfate–Ringer (+23 ± 4.6 μA, p < 0.01) than in chloride–Ringer (+14 ± 4.9 μA, p < 0.05). The increase in short-circuit current is approximately 0.9 μequiv. cm−2 h−1 in sulfate–Ringer, (iv) The increase in mean polarization is greater in chloride (+21 ± 6.2 mV, p < 0.02) than in sulfate (+6 ± 1.5 mV, p < 0.01) following a diphasic effect on potential, (v) Changes in apical impedance Z are small (−454 ± 323 Ω, nonsignificant) compared with transepithelial resistance in sulfate (−1065 ± 359 Ω, p < 0.05). (vi) Changes in membrane capacitance reflect changes in the membrane surface. However, no significant capacitance changes are produced in sulfate and chloride solution by heptaminol hydrochloride (−0.04 ± 0.11 μF and 0.05 ± 0.11 μF, respectively), (vii) Dielectric relaxation times, as indicated by off-centering in the impedance diagrams, are not affected significantly by heptaminol (−0.32 ± 0.95° in sulfate and +0.08 ± 0.9° in chloride), (viii) Time constants are shorter in sulfate (−0.44 ± 0.18 ms, p < 0.05), but are not significantly different in chloride (+0.13 ± 0.10 ms). (ix) Blockade of K+ channels by 5 mM Ba2+ prevents stimulatory effects of heptaminol. (x) Inhibitions of active transport with pharmacological (ouabain and (or) amiloride) and physical (cooling) agents can be attenuated by heptaminol hydrochloride. (xi) Sodium potential decreases (−99 ± 32 mV, p < 0.05) in contrast to an increase in parallel resistance (+31.44 ± 7.9 kΩ, p < 0.05). (xii) From these results, it is suggested that this molecule increases the membrane leakage resistance, in particular when the polarization is weak. It is suggested that an increase in cytosolic Ca2+ is likely to be involved.Key words: epithelium, frog skin, active transport, impedance measurement, resistance, heptaminol.
Effects of propafenone on sinus node function in the rabbit heart
Authors: Kerr Charles R.
Published: April 2011

Propafenone is a type 1C antiarrhythmic drug with efficacy for both ventricular and supraventricular arrhythmias. We investigated the effects of propafenone on properties of sinus node function in an in vitro preparation of rabbit sinus node and surrounding atrium. Spontaneous sinus cycle length (SCL), atriosinus conduction time (ASCT), and sinus node effective refractory period (SNERP) at multiple pacing cycle lengths were measured in the control state and during superfusion with propafenone (2.3 μM). SNERP prolonged from 175 ± 25 ms in the control state to 220 ± 45 ms (p < 0.001) with propafenone. ASCT also prolonged significantly (p < 0.01) from 50 ± 20 to 65 ± 20 ms whereas SCL did not change. In four experiments, multiple concentrations of propafenone were utilized and there appeared to be a dose-dependent prolongation of SNERP. Thus, propafenone has a significant effect on SNERP and ASCT in an isolated rabbit sinus node preparation.Key words: propafenone, sinus node, atrium.
Importance of neural input and thyroid hormones in the control of brown fat atrophy in mice
Authors: Desautels M. , Dulos R. A.
Published: April 2011

In euthyroid mice, a 48-h fast caused brown fat (BAT) atrophy characterized by loss of tissue proteins, succinate dehydrogenase (SDH), and a significant reduction in mitochondrial uncoupling protein (UCP) content. Chemical sympathectomy and surgical denervation failed to mimic the changes in BAT protein and SDH contents observed after food deprivation. However, suppression of sympathetic activity could account for the loss of UCP from the mitochondria. In mice made hyperthyroid by repeated triiodothyronine injections, losses of tissue SDH and proteins caused by food deprivation or surgical denervation were markedly suppressed, while the loss of UCP from the mitochondria remained unchanged. These results suggest that reduced sympathetic activity to BAT in fasted mice is not the exclusive cause of the tissue atrophy and that thyroid hormones may play a role in the control of brown fat atrophy in mice.Key words: brown adipose tissue, thermogenesis, uncoupling protein, energy balance, body weight, sympathetic nervous system.
Decrease in N-ethylmaleimide-sensitive ATPase activity in collecting duct by metabolic alkalosis
Authors: Garg Lal C. , Narang Neelam
Published: April 2011

Changes in systemic acid – base balance are known to influence acidification in the collecting duct. The H+ secretion in the collecting duct has been shown to be an electrogenic process and it has been suggested that an H-ATPase sensitive to inhibition by N-ethylmaleimide (NEM) is responsible for H+ secretion. This study was designed to determine the effect of metabolic alkalosis on NEM-sensitive ATPase activity in the microdissected segments of the distal nephron. Metabolic alkalosis was produced by giving NaHCO3 to normal rats for 7 days. The plasma total CO2 concentration in the experimental group was 31.5 ± 1.8 mM compared with 23.4 ± 1.0 mM in the control group. NEM-sensitive ATPase activity was significantly lower in the cortical collecting duct and in the outer and inner medullary collecting ducts of alkali-loaded rats than those of control rats. There was no significant difference in the enzyme activity between the two groups of animals in the other nephron segments examined. Our results suggest that NEM-sensitive H-APTase activity in all three segments of the collecting duct is modulated by the acid – base status of the animal.Key words: collecting duct, H-ATPase, electrogenic H-pump, metabolic alkalosis, rat kidney.
Modulation of stimulation frequency responses and calcium dependency of functional parameters in hyperthyroid rat ventricular papillary muscles
Authors: Seppet E. K. , Eimre M. A. , Kallikorm A. P.
Published: April 2011

The effects of stimulation frequency (0.2–1.5 Hz) and extracellular calcium concentration ([Ca2+]o) (0.6–15.0 mM) on the contractile function of thin papillary muscles of euthyroid and hyperthyroid rats were studied. Hyperthyroidism led to a decrease in developed tension (DT) and time to peak tension (TPT), but it exhibited no influence on the maximal rates of contraction (+dT/dt) and relaxation (−dT/dt). Also, the mean rates of contraction were similar in euthyroid and hyperthyroid muscle groups. The increase in stimulation frequency brought about a marked decrease in DT, +dT/dt, and −dT/dt of euthyroid papillary muscles at lower frequencies in comparison to papillary muscles in the hyperthyroid group. At stimulation frequencies above 1.0 Hz, the absolute and relative levels of DT and −dT/dt of hyperthyroid myocardium were elevated over euthyroid preparations. At the same time, TPT was unchanged in any of the muscle groups. Hyperthyroidism modulated the relationships between contractile parameters and [Ca2+]o. At a [Ca2+]o of 1.0–4.0 mM, the DT of hyperthyroid papillary muscles was lower than in euthyroid muscle. At 4.0 and 8.0 mM of [Ca2+]o, the equal values of maximal DT were registered for euthyroid and hyperthyroid papillary muscles, respectively. An increase in the [Ca2+]o in the range of 1.0–15.0 mM was accompanied by an increase in TPT of both muscle groups, but to a greater extent in hyperthyroid myocardium. In conclusion, the myocardium of hyperthyroid rat appeared to exhibit decreased sensitivity to calcium as well as to the negative inotropic effect of enhanced stimulation frequency. Alterations of the processes of transsarcolemmal movement and intracellular recycling of Ca2 may be implicated.Key words: euthyroid, hyperthyroid, myocardium, contractility, frequency, Ca2+ transport, sarcolemma, sarcoplasmic reticulum.
Reexamination of dopamine as the prolactin-release inhibiting factor (PIF): supplementary agent may be required for dopamine to function as the physiological PIF
Authors: Shin Seon H. , Hanna Samia F. , Hong Murray , Jhamandas Khem
Published: April 2011

A large number of studies have been performed concerning dopamine's inhibitory effect on prolactin release, but many of these studies have examined the effect of dopamine dissolved in a solution containing ascorbic acid. Ascorbic acid, routinely used to protect dopamine from oxidation, alone does not stimulate or inhibit prolactin release, but it can potentiate the inhibitory effect of dopamine in a static monolayer culture system by approximately 100 times. We have closely examined the inhibitory effect of dopamine on prolactin release in the absence of ascorbic acid using a perifusion system. Male rat adenohypophyses were dispersed with trypsin and cultured in a Petri dish to form cell clusters. Inhibition of prolactin release by dopamine (1 μmol/L) in the absence of ascorbic acid was sustained for only 63 min during the 2-h perifusion period. Following a 2-h period of incubation of dopamine in the same experimental solution, the dopamine concentration was reduced from 1 to 0.18 μmol/L, yet this "2-h-old dopamine" was still effective in inhibiting prolactin release (approximately 30 min). This result suggests that the lactotrophs may be desensitized by chronic exposure to a high concentration of dopamine in the absence of ascorbic acid. In contrast, when a low concentration of dopamine (3 nmol/L) containing ascorbic acid (0.1 mmol/L) was perifused, inhibition of prolactin release was sustained for the entire 2-h perifusion period. Although there may be a large number of explanations for dopamine's transient inhibitory effect on prolactin release, the present results suggest that dopamine may require supplementary agent(s) to effectively inhibit prolactin release and thus function as the prolactin release inhibitory factor (PIF). We propose ascorbic acid as a major candidate for the supplementary factor for the PIF.Key words: dopamine, somatostatin, prolactin, cell cluster, perifusion.
The interrelationship of cesium, intracellular sodium activity, and pacemaker potential in cardiac Purkinje fibers
Authors: Iacono Giovanni , Vassalle Mario
Published: April 2011

The actions of cesium (Cs) on intracellular sodium activity [Formula: see text], membrane potentials, and force were studied in sheep cardiac Purkinje and myocardial fibers superfused in vitro. In Purkinje fibers, Cs (2 mM) decreased diastolic depolarization, [Formula: see text] (−6.7%, p < 0.005), and force (−28.0%, p < 0.01). The effects of 4 and 8 mM Cs were more pronounced. In quiescent fibers, Cs (2–4 mM) also decreased [Formula: see text] (−17.3%, p < 0.005) and induced an initial hyperpolarization (+5.6 ± 1.3%, p < 0.005) followed by a return toward control. Diastolic depolarization was almost abolished by driving the fibers at 180/min (diastole was very short) but still Cs decreased [Formula: see text] (−15.4%). Tetrodotoxin decreased [Formula: see text] (−16.2%, p < 0.025) and reduced the Cs-induced fall in [Formula: see text] (−2.2%, p < 0.05). In zero [K]o, Cs decreased [Formula: see text] and caused repolarization. In 0.1 mM strophanthidin, Cs did not decrease [Formula: see text] any longer and affected the membrane potential little. In quiescent myocardial fibers, Cs (4 mM) decreased [Formula: see text] (−12.6%, p < 0.05) and transiently hyperpolarized (+2.1%). Rubidium (2 mM) decreased [Formula: see text] and resting potential in Purkinje fibers and in myocardial fibers and also decreased diastolic depolarization in Purkinje fibers. Thus, cesium and rubidium decrease [Formula: see text] and modify the membrane potential but not through a block of the inward pacemaker current If.Key words: rubidium, intracellular sodium activity, diastolic depolarization, tetrodotoxin, strophanthidin.
The direct depressant effect of LCB29 (idrocilamide) on mechanical tension of rat soleus muscle fibers
Authors: Bouron Alexandre , Rivet Michèle , Nasri-Sebdani Mohammad , Guillemain Joel , Durbin Philippe , Guerrier Daniel , Raymond Guy
Published: April 2011

The effect of LCB29 was tested on twitch characteristics, tetanic tension, and K+ and voltage-clamp contractures of rat soleus muscle fibers. In concentrations ranging from 10−6 to 5 × 10−4 M, LCB29 simultaneously inhibited the twitch amplitude, the maximum rate of tension development, and the maximum rate of relaxation. In concentrations ranging from 10−5 to 10−4 M, tetanic tension (100 Hz, 1 s) was inhibited by the same amount. The effect of 5 × 10−5 M LCB29 was studied on K+ contractures and contractures induced, under voltage-clamp conditions, by long-lasting depolarizations. Its effect was significantly stronger than those on twitch and tetanic tension. In addition, LCB29 had a dual effect on strength–duration curves for mechanical threshold. It increased both the rheobasic potential and the steepness of the curve. It is concluded that LCB29 exerts a direct myorelaxant effect on rat soleus muscle; two sites of action are probably involved.Key words: myorelaxants, skeletal muscle, K+ contractures, voltage clamp, mammalian.