bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage-dependent calcium fluxes in skeletal muscle transverse tubule membranes in the range of late afterpotentials
Authors: Öz A. Murat , Frank George B. , Dunn Susan M. J.
Published: April 2011

Calcium flux responses mediated by voltage-dependent calcium channels have been studied in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca2+, and membrane potentials were generated by establishing potassium gradients across the membrane in the presence of valinomycin. After the membranes were polarized to an estimated −80 mV to approximate the resting state of the cell, a significant 45Ca2+ efflux occurred upon subsequent depolarization to −60 mV. The efflux response was modulated by activators and inhibitors of slow, dihydropyridine-sensitive calcium channels, being inhibited by inorganic calcium channel blockers, verapamil, nifedipine, and (−)-SDZ 202 – 791 and potentiated by the dihydropyridine agonists (±)-Bay K8644 and (+)-SDZ 202 – 791. These results demonstrate that calcium channels in transverse tubule membranes can open to mediate calcium flux in the same range of membrane potential as the late afterpotentials that occur during tetanic contractions of intact muscle fibres.Key words: Ca2+ channels, dihydropyridines, skeletal muscle (rabbit), 45Ca2+ flux, late afterpotentials.
Neural effects of parathyroid hormone: modulation of the calcium channel current and metabolism of monoamines in identified Helisoma snail neurons
Authors: Wang R. , Pang P. K. T. , Wu L. , Shipley A. , Karpinski E. , Harvey S. , Berdan R. C.
Published: April 2011

Neuronal effects of parathyroid hormone (PTH) have been reported in vertebrates. The effect of PTH on invertebrate central neurons within the buccal ganglion of Helisoma trivolvis snails was examined in the present study. By using a vibrating probe, PTH was found to induce a transient calcium-dependent inward current in intact buccal ganglia. Intracellular micro-electrode recording revealed that PTH broadened the spontaneous action potential in buccal B5 neurons in situ. By using the whole-cell configuration of the patch-clamp technique, PTH was demonstrated to increase the N-like calcium channel currents in isolated B5 neurons in a concentration-dependent manner. This effect of PTH on the N-like calcium channel currents depended on the activation of a G protein insensitive to pertussis toxin, but was unlikely to be mediated by the cyclic AMP dependent protein kinase. Furthermore, the release of γ-glutamyl conjugate of dopamine from buccal ganglia was selectively increased in the presence of PTH. These results represent the first demonstration that a vertebrate peptide hormone, PTH, selectively modulates the N-like voltage-dependent calcium channel currents in identified invertebrate neurons. Therefore, a novel role of PTH in the regulation of invertebrate central neural functions is indicated.Key words: parathyroid hormone, patch clamp, vibrating probe, dopamine, invertebrate neuron.
Neuronal activity changes of ventromedial hypothalamic neurons and associated temperature responses in rats following scrotal thermal stimulation
Authors: Li Q. , Thornhill J.
Published: April 2011

Experiments were conducted to determine whether ventromedial hypothalamic (VMH) neurons were responsive to thermal warming or cooling of the scrotum. Extracellular neuronal activity of VMH neurons was monitored in anesthetized groups of normothermic (core temperature maintained at 37 °C) or hypothermic (core temperatures allowed to decrease, 33.3 ± 1.1 °C) male, Sprague–Dawley rats along with colonic (Tc), interscapular brown adipose tissue (TIBAT), tail (Tt), and scrotal (Tsc) temperatures during 30-min periods of scrotal cooling (small ice pack) or scrotal warming (small sealed pack containing 40 °C tap water). In the normothermic group (65 VMH neurons recorded in total), 20 VMH neurons (31%) were classified as warm-responsive neurons (WRNs) (i.e., increased firing rate with scrotal warming and (or) decreased firing rates with scrotal cooling); 7 VMH neurons (11%) were classified as cold-responsive neurons (CRNs) (i.e., increased firing rate with scrotal cooling and (or) decreased firing rate with scrotal warming); and 38 VMH neurons (58%) were thermal nonresponsive neurons (TNRNs). In the hypothermic group (total of 85 VMH neurons recorded), 14 neurons (16%) were WRNs, 15 neurons (18%) were CRNs, and 56 neurons (66%) were TNRNs. Results indicated that VMH neurons can respond selectively to changes in scrotal temperature, as previously shown for preoptic–anterior hypothalamic neurons. Scrotal cooling and warming caused marked changes in T(sc) values in both the hypothermic and normothermic rats, but significant increases in TIBAT values indicative of brown adipose tissue thermogenesis did not occur.Key words: ventromedial hypothalamic nucleus, extracellular neuronal recording, temperature, scrotum.
Luminal factors stimulate intestinal repair during the refeeding of malnourished infant rabbits
Authors: Philpott D. J. , Kirk D. R. , Butzner J. D.
Published: April 2011

We examined the role of luminal versus systemic factors in promoting intestinal recovery during the refeeding of previously malnourished infant rabbits. Malnutrition was induced by litter expansion at 7 days of age. A 20-cm Thiry–Vella (T-V) loop was created in the intestine of each malnourished and dietary control animal at 21 days of age. Beginning on day 28, controls and one half of the malnourished group (malnourished–refed) were fed chow ad libitum, whereas the remainder of the malnourished group received half the amount of chow given to the malnourished–refed group. On day 35, proximal and distal segments from the intact intestine that remained in continuity as well as segments from the excluded T-V loops were examined. Malnutrition severely reduced mucosal mass and disaccharidase activities in the intact distal intestine. A brief period of refeeding led to a rapid recovery of these parameters. In contrast, the excluded T-V loop segments of the control, malnourished, and malnourished–refed groups all displayed decreased mucosal mass and impaired function to a degree similar to that observed in the intact distal segment from the malnourished group. These results indicate that luminal factors are essential for (i) the maintenance of normal intestinal structure and function in infant rabbits and (ii) the promotion of mucosal repair following nutritional rehabilitation of malnourished animals.Key words: protein-energy malnutrition, intestinal adaptation, Thiry–Vella loop, refeeding.
Acute diabetes does not reduce heparin-releasable lipoprotein lipase activity in perfused hearts from Wistar–Kyoto rats
Authors: Rodrigues Brian , Severson David L.
Published: April 2011

The induction of diabetes (3–5 days duration) in Wistar–Kyoto rats by the administration of streptozotocin (100 mg/kg) did not increase plasma concentrations of triacylglycerols or free fatty acids, and did not reduce heparin-releasable (functional) lipoprotein lipase activity in perfused hearts. By comparison, diabetic Sprague–Dawley rats were characterized as having hypertriglyceridemia and decreased heparin-releasable lipoprotein lipase activity in perfused hearts. Therefore, the diabetes-induced reduction in myocardial lipoprotein lipase activity in Sprague–Dawley rat hearts may, at least in part, be a compensatory response to the hypertriglyceridemia and increased fatty acid delivery to the myocardial cell, which is a characteristic feature of most severe, insulin-deficient models of diabetes mellitus. Although functional, endothelium-bound lipoprotein lipase activity was not reduced in diabetic perfused hearts from Wistar–Kyoto rats, cellular and heparin-releasable lipoprotein lipase activity was reduced in cardiac myocyte preparations, suggesting that other mechanisms in addition to plasma triacylglycerol must regulate lipoprotein lipase activity in the whole diabetic Wistar–Kyoto rat heart and that cardiac myocytes may not be the exclusive source of functional lipoprotein lipase in the diabetic myocardium.Key words: diabetes, hypertriglyceridemia, lipoprotein lipase, perfused hearts, cardiac myocytes.
Effects of cesium on spontaneous rate in right atria isolated from diabetic rats
Authors: Kennedy Richard H. , Hicks Kristine K. , Stimers Joseph R. , Seifen Ernst
Published: April 2011

Previous studies have shown that streptozotocin (STZ) induced diabetes in rats is associated with a decrease in the spontaneous rate of isolated right atria. Present experiments were designed to determine whether this model of insulin-dependent diabetes mellitus alters the chronotropic actions of cesium (Cs+). Right atrial preparations were isolated from STZ-treated and diluent-treated control rats, and bathed in Krebs–Henseleit buffer at 37 °C; dose-dependent (0.2–10 mM) effects of Cs+ were examined by cumulative addition. Preparations isolated from diabetic rats had a slower beating rate before exposure to Cs+, and the negative chronotropic response to this cation was diminished in these tissues. In fact, at concentrations between 2 and 10 mM Cs+, spontaneous rate did not differ between the diabetic and control groups. These data suggest that the hyperpolarization-activated current, If, may play a role in the slower spontaneous pacemaker rate observed in right atria isolated from STZ-induced diabetic rats.Key words: cesium, heart rate, hyperpolarization-activated inward current, streptozotocin.
Developmental changes in the gonadotropin releasing hormone neuron of the female rabbit: effects of tamoxifen citrate and pregnant mare serum gonadotropin
Authors: Foster Warren G. , Jarrell John F. , YoungLai Edward V.
Published: April 2011

Developmental changes in immunostained gonadotropin releasing hormone neurons were demonstrated in female rabbits assigned to the following treatment groups: (i) tamoxifen citrate, 10 mg∙kg−1∙day−1, in sesame seed oil (vehicle) (n = 24) or (ii) vehicle alone (control, n = 24) for 108 days; and (iii) 50 IU of pregnant mare serum gonadotropin on postnatal days 22 and 25 (n = 24) or vehicle on nontreatment days. Treatments had no effect on the total number of immunostained cells, but there was a significant (p = 0.0160) developmental shift from cells with smooth processes to rough. Group comparisons revealed that there was a significant (p < 0.001) age-related increase in the number of rough cells in pregnant mare serum treated rabbits between days 25 and 75, indicating an advancement in the shift from smooth to rough cells. Plasma gonadotropin levels, ovarian follicular development, and the developmental shift from smooth to rough cells were markedly suppressed by tamoxifen treatment compared with rabbits of the control group, while no difference in estradiol levels were found. Our results suggest that a developmental shift in gonadotropin releasing hormone cell morphology from smooth to rough precedes sexual maturity in the female rabbit.Key words: development, sexual maturation, gonadotropin releasing hormone, puberty, immunohistochemistry.
Effects of the enantiomers of a new dihydropyridine derivative, S12968 and S12967, on renal functions in rats
Authors: López-Novoa José M. , Montañés Inmaculada
Published: April 2011

The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary sodium, potassium, and calcium excretions, mean arterial pressure, and renal vascular resistance were determined before and every 30 min up to 180 min after administration of the tested substance. The levogyre enantiomer S12968, at a dose of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without significant or with minor changes in glomerular filtration rate, renal plasma flow, or renal blood flow. The hypotensive effect was small and nonsignificant. At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal function, induced marked oliguria, and decreased glomerular filtration rate and renal blood flow to almost negligible values. The dextrogyre enantiomer S12967 had much less effect on renal function. These data showing specific stereoselective renal effects are in agreement with pharmacological studies that have demonstrated that S12968 possesses a higher affinity for the dihydropyridine-binding site than its dextrogyre enantiomer, S12967.Key words: Ca channel antagonists, dihydropyridine, glomerular filtration rate, renal blood flow, natriuresis, mean arterial pressure.
Predicting submaximal oxygen consumption during treadmill running in mice
Authors: Fernando P. , Bonen A. , Hoffman-Goetz L.
Published: April 2011

Treadmill exercise is the most common form of exercise used in studies involving laboratory rodents. However, oxygen consumption [Formula: see text] is not usually monitored since the measurement of this parameter is particularly difficult in small, exercising animals. The purpose of this study was to develop a regression equation for predicting submaximal [Formula: see text] in mice during treadmill running. Twenty female mice of three strains were tested, in an Oxyscan metabolic treadmill, on different days at running speeds of 10, 13, 15, 17, and 20 m/min at a 0% grade. Each mouse was placed in the treadmill chamber for a 10-min period before running commenced. Running speed was increased in 2-min intervals by 5 m/min until the assigned speed was reached. Each mouse then ran for 10 min to reach steady state, followed by another 20 min at the steady-state plateau. During this period a 30-s expired gas sample was collected every minute. Gas samples were analyzed for O2 and CO2, using an Oxyscan gas analyzer. Trials were conducted during the nocturnal phase of the animals' photoperiod, and running speeds were assigned randomly to minimize order effects. This approach provided highly reliable measures of oxygen consumption (r = 0.96). By using the running speeds (10–20 m/min) and the animal's body weight it was possible to predict the submaximal oxygen consumption (mL/min) during running with a high degree of accuracy (i.e., R2 = 0.85). In an independent group of animals (n = 14) we compared the predicted [Formula: see text] with the measured [Formula: see text]. This yielded a good correlation coefficient (r = 0.79) and a low prediction error (+2.4 ± 2.9%). This study demonstrated that it is possible to predict the submaximal oxygen consumption of laboratory mice during exercise, with an acceptable prediction error, from relatively simple measures (running speed and body weight). In addition, it was also possible to predict accurately the relative intensity of exercise [Formula: see text] using the animal's running speed on the treadmill (r = 0.999).Key words: submaximal [Formula: see text], treadmill exercise, regression equation, rodents.
Circadian rhythm of glycogen in the hamster diaphragm
Authors: Reid W. Darlene , Cairns Cheryl L. , Chung Frank , Wiggs Barry R. , Belcastro Angelo N.
Published: April 2011

The purpose of this study was to determine the diurnal fluctuation of glycogen stores for the whole hemidiaphragm and within a specific myofibrillar ATPase (M-ATPase) fibre type and diaphragmatic region. Fifty-six golden Syrian hamsters were randomly divided into six groups according to the time of sampling biopsies from the diaphragm: 03:00, 07:00, 11:00, 15:00, 19:00, and 23:00. The right hemidiaphragm was quick frozen and biochemically assayed for glycogen levels. Biopsies from the left hemidiaphragm of the same animal were cut from the anterior costal and crural regions, and stained with periodic acid – Schiff (PAS) and for M-ATPase. Optical density measures of PAS-stained fibres were determined to quantitate glycogen in different M-ATPase fibre types and diaphragmatic regions. Biochemical assay of the entire hemidiaphragm showed slightly greater glycogen content of biopsies taken at 11:00 and 15:00 than at 03:00, 19:00, and 23.00 (range of differences: 6.4–10.0%). However, glycogen levels within a specific M-ATPase fibre type and diaphragm region were not different in biopsies sampled at different times. Because the hamster has a small diurnal variation of glycogen in the diaphragm, which is similar to the small diurnal variation of glycogen in human skeletal muscle, this species may be a good animal model for metabolic studies of the diaphragm that could be affected by diurnal glycogen variability.Key words: periodic acid – Schiff, costal region, crural region, fibre type.
Effect of stimulus duty cycle and cycle frequency on power output during fatigue in rat diaphragm muscle doing oscillatory work
Authors: Stevens E. D. , Syme D. A.
Published: April 2011

Isolated rat diaphragm muscle was stimulated repetitively to induce fatigue, and the work done during each contraction was measured. Work per cycle was calculated by measuring force as the activated muscle was subjected to sinusoidal length changes (from 97 to 103% of L0, where L0 is rest length). Work was calculated from the loop formed when force was plotted against length. Work done was positive when the muscle was shortening and was negative when it was lengthening; net work was the difference. Work output was varied by changing the stimulus duty cycle (4, 8, or 16% of the total cycle duration) and cycle frequency (1, 2, or 4 Hz). The rate and extent of the decrease in power was influenced much more by changes in cycle frequency than by changes in duty cycle. Duty cycle and cycle frequency combinations that resulted in greater power in the prefatigue trials were associated with a more rapid rate of fatigue. However, net positive power at the end of the 15-min fatigue period was greater under these same conditions (i.e., high duty cycle and high cycle frequency). Fatigue in working diaphragm muscle depends more on cycle frequency than on duty cycle.Key words: skeletal muscle, muscle power, respiratory muscle, muscle lengthening.
Impaired spatial learning by vasoactive intestinal peptide in Morris water maze task in the rat
Authors: Itoh Shinji , Takashima Akira , Morimoto Taketoshi
Published: April 2011

Intracerebroventricular administration of vasoactive intestinal peptide (VIP) disturbed the learning by rats of the location of a platform submerged in a water pool. When the platform was removed from the pool, VIP injection produced marked impairment of the ability to find a previously learned location in the pool. This spatial memory impairment caused by VIP was restored by peripheral pre-administration of cerulein.Key words: vasoactive intestinal peptide, cerulein, Morris water maze task, memory, learning.
Electrical stimulation of the posterior and ventromedial hypothalamic nuclei causes specific activation of shivering and nonshivering thermogenesis
Authors: Thornhill J. A. , Halvorson I.
Published: April 2011

Experiments were designed to determine in the same animal whether electrical stimulation of the posterior hypothalamus and ventromedial hypothalamic nucleus could specifically evoke shivering and nonshivering (brown adipose tissue) thermogenesis, respectively, in anesthetized, normothermic rats. Urethane-anesthetized, male Long–Evans rats, kept at 37 °C, had colonic (Tc), gastrocnemius muscle (Tm), intrascapular brown adipose tissue (TIBAT), and tail (Tt) temperatures measured via thermistor probes, and electromyogram activity (differential multiunit activity from bipolar recording electrodes within gastrocnemius muscle) recorded, before and after unilateral electrical stimulation (monophasic 0.5-ms pulses of 200 μA at 50 Hz for 30 s) of the posterior hypothalamus and ventromedial hypothalamic nucleus (via stereotaxically implanted concentric stimulating electrodes). Each rat showed shivering (increased electromyogram activity) following posterior hypothalamic stimulation, which caused an immediate rise in Tm values with no change in TIBAT or Tt values. Electrical stimulation of the ventromedial hypothalamic nucleus of the same animals elicited no shivering activity, but significant increases in TIBAT values occurred with no change in Tm or Tt values. Results confirm that stimulation of the posterior and ventromedial hypothalamic nuclei in rodents specifically activates shivering and nonshivering (brown adipose tissue) effector mechanisms, respectively, to raise core temperature.Key words: posterior hypothalamus, shivering thermogenesis, ventromedial hypothalamus, intrascapular brown adipose tissue thermogenesis.
Delphinium alkaloids as inhibitors of α-bungarotoxin binding to rat and insect neural membranes
Authors: Kukel C. F. , Jennings K. R.
Published: April 2011

A series of C19-diterpenoid alkaloids purified from Delphinium were evaluated as inhibitors of α-bungarotoxin binding to rat and house fly neural membranes. In comparing these diterpenoid analogs, a wide range of inhibition potencies (IC50) were observed, with calculated IC50 values ranging six orders of magnitude. The most potent inhibitory alkaloids in this series possessed the succinimide aromatic ester moiety in the C18 position. Glaudelsine had an IC50 value of 42 pM at the insect nicotinic acetylcholine receptor.Key words: nicotinic, acetylcholine, delphinium, diterpenoid.
Selective interaction of chemical dyes with inositol 1,4,5-trisphosphate recognition sites
Authors: Richard Darren E. , Bernier Sylvie , Boulay Guylain , Guillemette Gaétan
Published: April 2011

Inositol 1,4,5-trisphosphate (InsP3) is an important second messenger that interacts with a specific intracellular receptor and triggers a release of Ca2+ from intracellular stores. InsP3 is preferentially metabolized by two enzymes. A specific 5-phosphatase (InsP3 phosphatase) produces an inactive metabolite, inositol 1,4-bisphosphate, while a specific 3-kinase (InsP3 kinase) produces an active metabolite, inositol 1,3,4,5-tetrakisphosphate. With the goal of developing selective ligands of the diverse InsP3 recognition sites, we have studied the effects of some chemical dyes on the binding of InsP3 to its receptor and on the activity of its metabolic enzymes. Although these dyes possess similar chemical structures, they showed varied selectivities towards the three recognition sites. Thymol Blue was the most potent inhibitor of InsP3 binding activity, with an IC50 of 105 μM. Phenol Red demonstrated a higher selectivity for InsP3 phosphatase inhibition, with an IC50 of 100 μM. 3′,3″,5′,5″-Tetraiodophenolsulfonephthalein showed its most potent inhibitory effect on InsP3 kinase activity, with an IC50 of 35 μM. Tetrabromophenol Blue potently inhibited InsP3 phosphatase and InsP3 kinase activities, with respective IC50 values of 25 and 12 μM. Phenolphthalein Diphosphate and Phenolphthalein Carbinol Disulfate demonstrated weak inhibitory effects towards the three recognition sites for InsP3. These results reveal certain structural clues that should help in the development of more selective inhibitors.Key words: structural analog, receptor, enzyme inhibitor, calcium, second messenger.
Neurokinin (NK2) receptors mediate nonadrenergic noncholinergic contractile responses to electrical stimulation and resiniferatoxin in guinea pig trachea
Authors: Charette Luc , Foulon Denise , Rodger Ian W. , Jones Thomas R.
Published: April 2011

In the present study we characterized the receptor(s) that mediates non-adrenergic non-cholinergic (NANC) contractions of isolated guinea pig cervical trachea, using CP-99,994, a selective neurokinin (NK1) receptor antagonist, and SR-48,968, a selective neurokinin (NK2) receptor antagonist. The activity of these two antagonists was determined against contractions to the selective agonists ([βAla8]NKA(4–10) for NK2 and [Sar9,Met(O2)11]SP for NK1) and the nonselective (SP and NKA) NK receptor agonists. CP-99,994 was inactive versus NKA and [βAla8]NKA(4–10) but antagonized SP- and [Sar9,Met(O2)11]SP-induced contractions with −log KB values of 5.6 ± 0.2 and 7.7 ± 0.2, respectively. SR-48,968 was inactive versus SP and [Sar9,Met(O2)11]SP but was active versus NKA and [βAla8]NKA(4–10), yielding −log KB values of 8.4 ± 0.2 and 9.1 ± 0.2, respectively. In the presence of 1 μM atropine, 1.4 μM indomethacin, 0.2 μM timolol, and 4 μM thiorphan, electrical field stimulation (16 Hz, 2.0 ms, 50 V for 10 every 30 min) elicited a NANC contractile response which was not significantly altered by CP-99,994 (3 μM) or the nitric oxide synthase inhibitor L-NAME (10 μM) but was completely inhibited by tetrodotoxin (TTX) (1 μM) and was also reduced to 58 ± 12, 31 ± 16, 8 ± 4, and 0% of control by 15, 50, 150, and 1500 nM SR-48,968, respectively. Resiniferatoxin (1 and 10 nM) produced a well-maintained concentration-dependent contraction, which was 57.8 ± 4.8 and 61.6 ± 3.8%, respectively, of the carbachol-induced maximum response. Contractions were not significantly modified by L-NAME and were not blocked by TTX (1 μM). SR-48,968 (150 nM) almost completely blocked the contractile response to 1 and 10 nM resiniferatoxin. CP-99,994 (0.3 μM) was inactive when tested alone but blocked the residual response in the presence of SR-48,968. It is concluded that TTX-sensitive NANC contractions to electrical field stimulation of guinea pig trachea are mediated by neurokinins acting primarily on NK2 receptors. Resiniferatoxin produces much more profound NANC contractile responses, which are not modified by TTX and are mediated by tachykinins acting to a large degree on NK2 receptors and, to a minor degree, on NK1 receptors.Key words: NK1 and NK2 antagonists, electrical stimulation, resiniferatoxin, guinea pig trachea.
Epithelial modulation of cholinergic responses in human tracheal smooth muscle
Authors: Bai Tony R. , Prasad F. W. F.
Published: April 2011

The aim of this study was to test the hypothesis that the increase in maximal responses to histamine, acetylcholine, and cholinergic electrical field stimulation and decreased relaxant responses to isoprenaline reported in asthmatic tracheal smooth muscle result from the epithelial damage observed in asthma. The effect of mechanical removal of the epithelium on contractile and relaxant responses was examined in normal human postmortem tracheal smooth muscle strips. The epithelium was removed from alternate tracheal strips obtained from 25 subjects within 14 h of sudden death from nonrespiratory causes. In paired samples, contractile cholinergic and inhibitory nonadrenergic, noncholinergic (i-NANC) neural responses to electrical field stimulation and responses to exogenous histamine, potassium chloride, theophylline, and isoprenaline were unaffected by removal of the epithelium. However, the maximal isometric tension (Tmax) induced by methacholine increased by 70.1 ± 19.8% (mean ± SE, p < 0.005, n = 9), without alteration in EC50. These data suggest that disruption of the epithelium is unlikely to be the explanation of the abnormalities observed in trachea in fatal asthma. Explanations of the increase in maximal response to methacholine following removal of the epithelium include loss of an epithelium-derived relaxant factor released via an epithelial muscarinic receptor or loss of a specific permeability or metabolic barrier imposed by the epithelium for methacholine.Key words: asthma, epithelium-derived relaxant factor, airway responsiveness, airway innervation.
ICS 205-930 reduces 5-methoxytryptamine-induced short-circuit current in stripped pig jejunum
Authors: Hansen Mark Berner
Published: April 2011

The effect of ICS 205-930 on serotonin (5-hydroxytryptamine, 5-HT) and 5-methoxytryptamine (5-MeOT) induced short-circuit current (SCC) was studied in muscle-stripped pig jejunum in vitro. The selective 5-HT4 receptor agonist 5-MeOT and 5-HT both induced a concentration-dependent increase in SCC. The maximal efficacy of 5-HT was twice that of 5-MeOT. ICS 205-930 (Tropisetron) induced a small increase in SCC. Furthermore, ICS 205-930 reduced the 5-MeOT but not the 5-HT induced increase in SCC, except at the 100 μM ICS 205-930 concentration. Pretreatment with bumetanide reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 64, 75, and 58%, respectively. Pretreatment with atropine reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 38, 75, and 58%, respectively. Pretreatment with hexamethonium reduced 5-HT, 5-MeOT, and ICS 205-930 induced peak increases in SCC by 33, 50, and 36%, respectively. Pretreatment with tetrodotoxin reduced the peak increase in SCC elicited by 5-MeOT and ICS 205-930 by 41 and 50%, respectively. This study demonstrates involvement of a ICS 205-930, hexamethonium, atropine, bumetanide, and tetrodotoxin sensitive receptor in 5-MeOT induced SCC in muscle-stripped pig jejunum in vitro. These data suggest involvement of a neuronal 5-HT4 receptor subtype and acetylcholine in 5-HT elicited SCC and chloride secretion in the pig jejunum.Key words: intestinal secretion, 5-hydroxytryptamine, 5-methoxytryptamine, jejunum, antagonists, pig, Tropisetron, ICS 205-930.
Platelet adhesion, shape change, and aggregation: rapid initiation and signal transduction events
Authors: Gear Adrian R. L.
Published: April 2011

Blood platelets are essential for hemostasis, and knowledge of their function is important for understanding both normal and pathologic situations. A number of approaches have been used to evaluate platelet adhesion, aggregation, and secretion, and within the last 10 years much interest has been directed to the biochemical mechanisms and signal transduction events occurring during these various phases of function. New information has come from development of technologies to evaluate the changes occurring immediately after platelet activation and consistent with the speed needed for hemostasis in the arterial circulation. Use of rapid flow and mixing technologies as seen in quenched-fiow, continuous-flow, and stopped-flow devices has revealed that platelet aggregation, shape change, adhesion, and secretion begin within 1 s and may be nearly complete by 5 s. Biochemical changes such as in protein phosphorylation, calcium release, and phospholipid hydrolysis are clearly evident in hundreds of milliseconds. Therefore, it is necessary to understand these early events in signal transduction and to assess alterations that may occur in diseases such as diabetes.Key words: platelets, quenched flow, aggregation, adhesion, inositol.
Analysis of strneture–fonction relationships in human apolipoprotein(a)
Authors: Hoek Ytje Y. van der , Kastelein John J. P. , Koschinsky Marlys L.
Published: April 2011

Elevated levels of lipoprotein(a) (Lp(a)) have been strongly correlated with the development of atherosclerosis in human populations. Lp(a) is distinguishable from low density lipoprotein by the presence of the unique protein component apolipoprotein(a) (apo(a)), which contains repeated domains that closely resemble that of plasminogen kringle IV. Using human embryonic kidney cells, we have expressed a recombinant form of apo(a) (r-apo(a)) containing 17 kringle IV-like domains. We have utilized this recombinant expression system to study the assembly of Lp(a) particles. We have demonstrated that Lp(a) particles containing r-apo(a) can be assembled extracellularly in plasma by covalent linkage to low density lipoprotein. Using site-directed mutagenesis, we have demonstrated that a cysteine residue present at position 4057 of the apo(a) protein (i.e., in the penultimate kringle IV repeat) mediates this covalent linkage. Using polymerase chain reaction amplification of liver apo(a) complementary DNA, we have demonstrated the presence of a polymorphism in apo(a) kringle IV type 10, which results in the substitution of a threonine for a methionine. Preliminary studies indicate that the presence of a threonine at this position may enhance the interaction of Lp(a) with lysine–Sepharose.Key words: apolipoprotein(a), lipoprotein(a), kringles, lipoprotein(a) assembly, polymorphism.
Bioactive substances in food: identification and potential uses
Authors: Kitts David D.
Published: April 2011

Bioactive substances in foods can represent "extranutritional" constituents naturally present in small quantities in the food matrix, produced upon either in vivo or industrial enzymatic digestion, the latter being a result of food-processing activities. Bioactive constituents of food evoke physiological, behavioral, and immunological effects. Evidence from both epidemiological and animal studies has suggested chemopreventative roles for phytochemicals in certain forms of cancers and in the control of hyperlipidemia. Secondary products of plant metabolism can modulate xenobiotic metabolizing and cholesterol synthetic enzymes. Unique physicochemical properties of food-derived peptides with characteristic amino acid composition and sequences have been reported to influence intestinal transit, modify nutrient absorption and excretion, and exhibit immuno-stimulating and antihypertensive activity. Biologically active peptides derived from casein, fish muscle, and plant protein hydrolysates have been isolated, purified, and identified in peptide sequence studies. Therapeutic proteins (e.g., specific antibodies) derived from animal products such as milk may offer the potential for developing specialized food products with prophylactic as well as nutritive quality. This paper discusses the physicochemical mechanism of action of specific bioactive substances naturally present in or derived from foods. The biotechnologies employed to develop these products and the issues concerning acceptance by consumer and regulatory bodies are also addressed.Key words: bioactive substances, food, biotechnology, nutrition.
Cutaneous neural codes for shape
Authors: Lamotte Robert H. , Srinivasan Mandayam A. , Lu Charles , Klusch-Petersen Andreas
Published: April 2011

In the pursuit of peripheral neural representations of shape for the sense of touch, a series of two- and three-dimensional objects were stroked across the fingerpad of the anesthetized monkey and responses evoked in cutaneous mechanoreceptive primary afferent nerve fibers recorded. Responses of slowly adapting fibers (SAs) and rapidly adapting fibers (RAs) were recorded to the stroking of a cylinder, a sphere, several ellipsoids, and a pattern of alternating convex and concave cylindrical bars. The compressional force was maintained constant during a stroke, and the stroke velocities as well as orientations of the objects and stroke trajectories were varied between separate sets of trials. The major geometrical properties of the shapes were well represented in the spatiotemporal responses of the afferent fiber populations, particularly those of the SAs. Intensive parameters of shapes, such as the magnitude of change in skin curvature produced as a result of contact with the object surface, were encoded in the discharge rates of SAs and RAs, but this neural code was also influenced by changes in stroke velocity. Spatial parameters of shapes such as the extent of contact and the changes in contour that characterize a shape as belonging to a particular category (such as a sphere as opposed to a cylinder) are encoded in the spatially distributed discharge rates of the SA population. This spatial response profile provides a neural code that is probably invariant with moderate changes in the way the object comes in contact with the skin, such as the contact force or the orientation of the object.Key words: shape, cutaneous mechanoreceptors, primates, touch.
The hand and the object: the role of posterior parietal cortex in forming motor representations
Authors: Jeannerod M.
Published: April 2011

The hypothesis of several subsystems for processing visual information is expanded to the context of visuomotor functions. It is proposed that object-oriented actions involve three main types of processing whether the object is to be localized, identified, or grasped and manipulated. Neurological evidence from patients is provided, showing that each type of processing pertains to a distinct pathway. Whereas identification is impaired by lesions affecting the occipitotemporal pathway, localization and grasping are processed in posterior patrietal cortex. A new clinical case with a parietal lesion is presented, where the grasping deficit contrasted with preservation of both identification and localization. This result suggests separate representations for localizing and grasping within parietal cortex.Key words: visuomotor coordination, hand movements, parietal cortex, neuropsychology.
Some shear facts and pure friction related to roughness discrimination and the cutaneous control of grasping
Authors: Smith Allan M.
Published: April 2011

The question of whether friction contributes to the perception of roughness has been overdebated and underinvestigated. A review of the psychophysical literature suggests that roughness and friction can be subjectively distinguished very effectively, although the same rapidly adapting Meissner corpuscles (RA1s) and slowly adapting Merkel receptors (SA1s) are stimulated by both stimuli. It appears that to achieve the subjective appreciation of roughness, the brain must learn to ignore variations in the speed of movement over the skin, the perpendicular force applied to the receptor surface, and the shear forces tangential to the skin generated by friction. Similarly, the subjective appreciation of slipperiness requires selective attention to tangential forces to the exclusion of speed, perpendicular force, and surface texture. A clearer picture is gradually emerging concerning the detection and appreciation of shear forces from investigations of the grasping and lifting of objects of different surfaces against the force of gravity. Although high shear forces provoke larger responses in almost all skin mechanoreceptors, some neurons in both the sensory and motor cortex discharge more vigorously with smooth textures and lower coefficients of friction. Although populations of such neurons sensitive to smooth surfaces and low friction would be very useful in detecting both potential and real slips, just how the afferent signals are derived remains puzzling.Key words: cutaneous sensation, friction, grip force, roughness, shear force, surface texture.
Angiotensin II induced alteration of cyclic adenosine 3′,5′-monophosphate generation in the hypertrophic myocardium of Dahl salt-sensitive rat on a high-salt diet
Authors: Sunga Paul S. , Rabkin Simon W.
Published: April 2011

The objective of this study was to explore the action of angiotensin II (AII) on cardiac contractility and cyclic AMP (cAMP) generation by forskolin and isoproterenol in the hypertrophic myocardium of the salt-sensitive Dahl rat. Inbred Dahl S and Dahl R rats that had been on a diet supplemented with 6% NaCl were studied. The functional effects of the interaction of AII and forskolin on cardiac contractility were assessed in the isolated heart preparation. The effect on the cAMP signal transduction pathway was assessed in cardiomyocytes isolated from hearts of Dahl S and R rats. Dahl S rats developed cardiac hypertrophy on a high-salt diet, whereas Dahl R rats did not. Forskolin increased cardiac contractility, which was differently affected by AII, depending on whether the heart was from hypertrophied Dahl S rat or from the control Dahl R rat. All accentuated forskolin-induced increases in cardiac contractility in hypertrophic hearts but diminished forskolin-induced increases in contractility in the nonhypertrophied hearts. This response was reflected in the cAMP response to forskolin, in that AII decreased forskolin-induced increases in cAMP in the nonhypertrophic heart. AII had the reverse effect in cardiomyocytes from hypertrophied hearts, as AII increased forskolin-induced cAMP production. This was shown to be due to an AII receptor mediated effect, as it was antagonized by the AII receptor antagonist saralasin. The same effects of AII were found on isoproterenol-induced increases in cAMP. Similar results occurred in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), suggesting that the effect was on cAMP production rather than cAMP degradation. This was attributed to an inhibitory G protein (Gi) mechanism, as the muscarinic agonist carbachol, which acts through Gi, produced the same effects as AII Furthermore, the effects of AII were abolished by pertussis toxin, which inactivates Gi. These data indicate a reversal of control by AII in the hypertrophic Dahl S heart in response to forskolin, which activates adenylyl cyclase directly on the catalytic subunit, converting the substrate, ATP, to cAMP, independent of the guanine nucleotide activated protein, and in response to isoproterenol, which activates adenylyl cyclase through G protein mechanisms. AII accentuated the forskolin-induced increase in cardiac contractility and cAMP generation in the hypertrophied ventricle but decreased both contractility and cAMP generation in nonhypertrophied hearts, suggesting that the process of cardiac hypertrophy in salt-sensitive Dahl rat may compensate for the reduction in intracellular cAMP by altering its regulatory control by AII.Key words: cardiac hypertrophy, angiotensin, forskolin, isoproterenol, adenylyl cyclase, Dahl rat.
Investigation of the role of oxidative stress in amiodarone-induced pulmonary toxicity in the hamster
Authors: Leeder Randall G. , Brien James F. , Massey Thomas E.
Published: April 2011

Associated with amiodarone (AM) therapy is pneumonitis, which may progress to life-threatening pulmonary fibrosis. Although the etiology of amiodarone-induced pulmonary toxicity (AIPT) is unknown, a role for direct toxicity by oxidative stress has been proposed. We have used a single intratracheal administration of AM (1.8 mg (2.64 μmol)) to male golden Syrian hamsters to investigate the role of oxidative stress in AIPT. The antioxidant capacity of the lung was assessed following AM administration by evaluating glutathione status and antioxidant enzyme activities. The efficacy of treatment with the antioxidant agents butylated hydroxyanisole, diallyl sulfide, and N-acetylcysteine, in attenuation of AM-induced pulmonary fibrosis was also investigated. AM significantly (p < 0.05) increased the ratio of oxidized to total lung glutathione both 30 min (control, 0.93 ± 0.23%; AM, 2.06 ± 0.26%) and 120 min (control, 0.90 ± 0.21%; AM, 3.58 ± 1.34%) post administration. AM also increased activities of glutathione reductase (by 89%) 3 days post administration, and glutathione peroxidase (by 110 and 45%, respectively) and total superoxide dismutase (by 58 and 35%, respectively) both 3 and 7 days post administration. However, treatment of hamsters with butylated hydroxyanisole (150 mg∙kg−1∙day−1 s.c.) or diallyl sulfide (200 mg∙kg−1∙day−1, p.o.) for 3 days prior to AM, or treatment with N-acetylcysteine (10 mg intratracheally) 10 min prior to AM had no effect on pulmonary fibrosis 21 days post treatment, as determined by lung wet weight and hydroxyproline content, and had inconsistent effects on histologically determined disease index. The alterations in glutathione status and antioxidant enzyme activities are consistent with an oxidant mechanism for AIPT, although prior treatment with the selected antioxidant agent regimens was ineffective in attenuating lung injury.Key words: amiodarone, oxidative stress, lung, fibrosis, hamster.
Blood pressure control and erythrocytosis in rats: theory and observations
Authors: Gould Anne B. , Goodman Susan , Swartz Charles
Published: April 2011

We compared some of our latest experiments on blood pressure control and erythrocytosis in spontaneously hypertensive rats with Gaar's computer-simulated studies, which suggest that erythrocytosis is a key to understanding the hemodynamic changes in hypertension. We tested two of Gaar's several predictions: (i) peripheral vascular resistance decreases when the feedback control of erythrocytosis is blocked and (ii) in primary hypertension, blood volume is increased slightly. We also studied the interrelation of systolic blood pressure and plasma renin substrate in spontaneously hypertensive rats, and the effect of diet on renin, blood pressure, and erythrocytosis. Our data showed that (i) on a percentage basis the renin system supports blood pressure essentially in the same manner in normal and hypertensive rats, (ii) peripheral vascular resistance decreased when erythrocytosis was partially blocked by feeding a low-iron diet, (iii) blood volume was similar in normal and hypertensive rats, and (iv) dextrin stimulates plasma renin, packed cell volume, and blood pressure in hypertensive rats. We conclude that blood pressure and erythrocytosis are interrelated, that the combined data of simulated and experimental studies support the notion that primary hypertension is a blood-vessel adaptation in response to a renal energy need that may require additional oxygen.Key words: angiotensinogen, renin, dextrin, packed cell volume.
Comparison of calcium absorptive and secretory capacities of segments of intact or functionally resected intestine during normo-, hypo-, and hyper-calcemia
Authors: Krishnamra N. , Angkanaporn K. , Deenoi T.
Published: April 2011

Absorptive and secretory capacities of six in situ intestinal loops of equal length were compared under the same calcium load and calcemic condition. The highest rate of calcium absorption was found in duodenum, colon, and proximal jejunum when loops were filled with 0.3 mM calcium, and in duodenum and proximal jejunum when filled with 10 mM luminal calcium. Secretory rates were in the following order: duodenum, jejunum, proximal jejunum, cecum, ileum, and proximal colon. Absorption of 0.3 mM calcium was decreased in all but the cecum and colon during hypercalcemia, and in duodenum, proximal jejunum, and colon during thyroparathyroidectomy-induced hypocalcemia. In contrast, calcium secretion was directly related to plasma calcium concentration and the length of the intestine. Functional resection of any part met with a compensatory increase in calcium absorption by the remaining segments, with the exception of the resection of the distal ileum with the large bowel. In conclusion, proximal small intestine exhibited the highest rate of absorption and secretion, but functional resection of this or any part did not affect the overall calcium absorption if luminal calcium was 10 mM. Moreover, enhanced secretion and reduced absorption during hypercalcemia were beneficial with respect to plasma calcium regulation.Key words: calcium, hypercalcemia, hypocalcemia, intestinal absorption, intestinal secretion.