bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation, distribution, and plasticity of atrial natriuretic factor binding sites in brain
Authors: Quirion Rémi , Dalpé Michel , DeLéan André
Published: April 2011

The [125I]iodotyrosyl derivative of atrial natriuretic factor ([125I]ANF) apparently binds to a single class of high affinity sites in guinea pig brain membrane preparations. Ligand selectivity pattern reveals that the structural requirements of brain [125I]ANF binding sites are similar to those reported in most peripheral tissues. In vitro receptor autoradiographic studies demonstrate that the brain distribution of [125I]ANF binding sites is species dependent. In rat, high levels of binding are found in olfactory bulb, subfornical organ, area postrema, choroid plexus, and ependyma. In guinea pig, these regions are also enriched with [125I]ANF binding in addition to various thalamic nucleic, amygdala, hippocampus, and cerebellum. In monkey, high densities of sites are seen in the cerebellar cortex. This suggests that brain ANF receptor sites could mediate ANF effects related to the central integration of cardiovascular parameters, as well as other actions not associated with these systems. As in the periphery, it appears that brain [125I]ANF binding sites are associated with guanylate cyclase. Moreover, the density of [125I]ANF receptor binding sites is altered in certain brain regions in spontaneously hypertensive rats and in cardiomyopathic hamsters, demonstrating the plasticity of brain ANF receptors. Thus, ANF and ANF receptors are complementary facets of a new neurotransmitter–neuromodulator system present in mammalian brain.
Natriuretic and diuretic action of centrally administered rat atrial natriuretic peptide (99–126): possible involvement of aldosterone and the sympathoadrenal system
Authors: Israel Anita , Torres Marysabel , Barbella Yarisma
Published: April 2011

Intracerebroventricular (ICV) administration of rat atrial natriuretic peptide (99–126) (rANP) to conscious male hydrated rats resulted in a dose-related increase in urinary volume and sodium excretion over a 6-h period of urine collection. A diminished mineralocorticoid effect on the kidneys may explain the natriuretic phenomenon. This hypothesis was tested by ICV rANP injection (1.25 μg/5 μL) in conscious hydrated rats pretreated beforehand with d-aldosterone (20 μg/kg, ip). Although the absolute amount of sodium excreted was reduced, aldosterone did not affect rANP-induced sodium output at 1 and 3 h. Rats that were sham-operated or bilaterally adrenalectomized after 4 days were pretreated with aldosterone and given an oral water load followed by ICV rANP or saline. The possible participation of the peripheral sympathetic nervous system in the central action of rANP was evaluated in rats pretreated with 6-hydroxydopamine. In sympathectomized and adrenalectomized rats natriuresis and diuresis were still evident after rANP. Our results indicate that the natriuretic effect of ICV rANP is independent of mineralocorticoids. Likewise, diuresis and natriuresis can occur in the absence of the adrenal glands and are independent from the neural tone that the adrenergic system exerts on sodium reabsorption.
Rapid measurement of blood ethanol concentrations using the alcohol oxidase membrane technique
Authors: Greenway C. V. , Pushka K. , Sitar D. S. , Rogers L. K.
Published: April 2011

The alcohol oxidase membrane technique is available for measurement of ethanol in commercial fluids. In this paper we examined its usefulness for cat and human blood in comparison with gas–liquid chromatography (GLC). The membrane method proved to be simple, reproducible, accurate, and inexpensive. Analysis took 1–2 min per sample and required only 25 μL of whole blood for measurement of concentrations between 0.05 and 1.0 mM (0.25–5 mg/dL) and 10 μL of whole blood for measurement of concentrations between 1.0 and 40 mM (5–190 mg/dL). Background concentrations were undetectable in cats after extraneous sources of alcohols were removed. The alcohol oxidase membrane technique is less specific than GLC, but it may be useful when ethanol is administered after background samples have shown an absence of other nonspecific reactants. Its high sensitivity is useful for kinetic studies where blood ethanol concentrations are below or close to those required for maximal hepatic ethanol metabolism.
Binding of 125I-labelled human chorionic gonadotropin to cell membrane receptors in rabbit ovarian slices
Authors: YoungLai E. V. , Wilkinson M. , Hibbert P. , McMahon A. , Jarrell J. F.
Published: April 2011

The binding of 125I-labelled human chorionic gonadotropin (HCG) was studied using thick slices (300 μm) of rabbit ovarian tissue. Binding was saturable, reversible, stereospecific, and of high affinity. The amount of binding was proportional to the number of slices used and could be destroyed by boiling. Ovarian slices from eight individual rabbits were found to have two binding sites for 125I-labelled HCG with KD values of 272 ± 64 and 1263 ± 274 pM and Bmax values of 25.7 ± 5.3 and 94.1 ± 18.8 fmol/mg protein, respectively. In a comparative study the KD and Bmax values were 351 ± 151 pM and 25.3 ± 11.1 fmol/mg protein with slices from one ovary and 134 ± 24 pM and 109 ± 32 fmol/mg protein with membranes from the contralateral ovary. These data suggest that the binding of HCG can be determined in live tissue.
Hemorrhage with blood reinfusion and the relationship between gastroduodenal motility and bile reflux in rats
Authors: Limlomwongse Liangchai , Suanarunsawat Tamonwan , Krishnamra Nateetip
Published: April 2011

The relationship between gastroduodenal motility and bile reflux was studied in normal rats and in rats subjected to hemorrhage and blood reinfusion. Bile secretion decreased from 5.3 ± 0.4 to 4.1 ± 0.5 μL/(min∙100 g rat) (p < 0.05) during the hypovolemic stress and recovered after blood reinfusion. Gastric bile salt content was low (0.1 ± 0.03 μmol/(h∙100 g rat)) during control period and hemorrhage but increased to 0.7 ± 0.12 μmol/(h∙100 g rat) (p < 0.001) during the 3 h folio wing blood replacement. Marked gastric and duodenal retention of polyethylene glycol was observed immediately after hypovolemia with the former being evident even after 3 h following blood reinfusion, while duodenal emptying recovered rapidly after reinfusion. The frequency of gastric contraction remained unchanged during hemorrhage but decreased after 90 min following blood replacement, whereas the frequency of duodenal contraction abruptly decreased during hemorrhage and recovered after reinfusion. Both gastric and duodenal contractile pressure was significantly decreased during hemorrhage. After reinfusion, the former remained suppressed while the latter was fully recovered within 1 h. Thus, a significant duodenogastric bile reflux observed after reinfusion was due to a higher duodenal contractile pressure, and the uncoordinated gastroduodenal motility with the duodenal motility fully recovered soon after reinfusion while that of the stomach remained suppressed.
Measurement of branched chain amino acids in blood plasma by high performance liquid chromatography
Authors: Robitaille Line , Hoffer L. John
Published: April 2011

A simple and rapid high performance liquid chromatographic technique is described for the separation and quantitation of plasma branched chain amino acids. After addition of a norleucine internal standard, plasma samples are acidified with acetic acid, and amino acids are separated from proteins and other plasma components by passage of the acidified plasma through an ion exchange resin. The ammonium hydroxide eluate from the resin is dried, phenylisothiocyanate derivatives are prepared, and the amino acids are separated on a Waters reverse-phase "Pico-Tag" column with an ultraviolet detector set at 254 nm. In addition to the branched chain amino acids (leucine, valine, and isoleucine), aspartate, glutamate, serine, threonine, alanine, and methionine are quantitated with high precision and accuracy, as verified by quantitative recovery and comparison with an automatic amino acid analyzer. The advantages of the method are its simplicity, speed, stability of derivatives, high reproducibility, low per-sample cost, and the use of a simple fixed-wavelength ultraviolet detector.
Diabetes-induced rat tracheal segment supersensitivity to carbachol
Authors: Mongold J. J. , Gros G. H. , Michel A. , McNeill J. H. , Serrano J. J.
Published: April 2011

Contractile responses to carbachol of tracheal segments isolated (i) from rats made diabetic 4 months prior by a single intravenous injection (50 mg/kg) of streptozotocin (group B), and (ii) from diabetic rats that had been treated during the same period with a daily dose (2–4 U/animal) of long-acting insulin (group C) were compared with the contractile responses of trachea isolated from age-matched control animals (group A). Tracheal segments from group B were significantly more responsive to carbachol than those from group A or C at low, but not at high carbachol concentrations. Carbachol pD2 values were higher in group B (6.85 ± 0.05) than in groups A (6.46 ± 0.07) or C (6.37 ± 0.06), but were not significantly different between groups A and C. These data indicate that diabetes induces a supersensitivity to carbachol in airway smooth muscles, possibly related to a diabetes-induced vagal autonomic neuropathy.
Effects of albumin on fatty acid, protein, and eicosanoid levels in rat mesenteric arterial bed perfusions
Authors: Jenkins D. Kenneth , Mitchell Janet C. , Manku Mehar S. , Horrobin David F.
Published: April 2011

Male rats were maintained on rat chow supplemented with 5% evening primrose oil for 2 weeks. Mesenteric perfusions were then performed, half with and half without albumin. Albumin was found to increase the yield of fatty acids and reduce eicosanoid levels. Perfusions without albumin decreased fatty acid release, increased eicosanoid levels, and showed a decrease in protein concentration over time. The value of albumin as a "trap" for fatty acids during perfusion experiments depends upon what parameter is to be measured.
Proximal and distal tubular activity in chronically catheterized fetal sheep compared with the adult
Authors: Lumbers Eugenie R. , Hill Karen J. , Bennett Victoria J.
Published: April 2011

Renal function was studied in unanaesthetized fetal sheep aged 112–120 and 126–132 days and in adult nonpregnant ewes. The clearance of lithium was used to measure proximal and distal fractional sodium reabsorption. In five nonpregnant adult sheep, 80.6 ± 1.7% (SE) of the filtered sodium load was reabsorbed proximaily and 18.2 ± 1.53% distally. This was different from all groups of fetal sheep (p < 0.001). In younger fetuses, proximal fractional sodium reabsorption was less (51.3 ± 2.3% (SE), p < 0.05) and distal fractional sodium reabsorption greater (42.4 ± 2.3% (SE), p < 0.05) than older fetuses (126–132 days old) in which 61.4 ± 2.4% (SE) was reabsorbed proximaily and 33.6 ± 2.5% (SE) distally. In another group of fetuses aged 125–137 days, in which proximal tubular sodium reabsorption was measured after distal tubular blockade, proximal fractional sodium reabsorption was 57.8 ± 2.95% (SE) and distal fractional sodium reabsorption, 38.7 ± 2.64% (SE). In adult sheep there was no relationship between distal tubular sodium reabsorption and glomerular filtration rate, i.e., proximal tubular function was responsible for glomerulotubular balance. However, in the fetuses, both proximal and distal tubular sodium reabsorption contributed to glomerulotubular balance. Thus in fetal life, the proximal tubule participates to a lesser extent in reabsorbing the filtered sodium load possibly because its function is suppressed by its relatively "volume-expanded" state or because it is functionally immature. Therefore, a greater proportion is reabsorbed distally and the distal nephron participates under physiological conditions in glomerulotubular balance.
Absence of staircase following disuse in rat gastrocnemius muscle
Authors: MacIntosh Brian R. , Roberge Marie-Cristine , Gardiner Phillip F.
Published: April 2011

Repetitive stimulation of mammalian fast-twitch skeletal muscles will normally result in a positive staircase response. This phenomenon was investigated in the rat gastrocnemius muscle following a 2-week period of tetrodotoxin-induced disuse. Muscle inactivity was imposed by superfusing tetrodotoxin in saline over the left sciatic nerve via an implanted osmotic pump. In situ isometric contractile responses to double pulse stimulation and repetitive stimulation at 10 Hz were determined the day after removal of the pump. Two weeks of disuse resulted in 40% muscle weight loss. A twitch contraction gave the same force when expressed per gram of wet muscle weight in control muscles, 317 ± 24.6 [Formula: see text] g/g, as compared with tetrodotoxin-treated muscles, 328 ± 24.2 g/g. Both contraction time and half-relaxation time were prolonged following treatment with tetrodotoxin. Repetitive stimulation at 10 Hz resulted in a positive staircase response in the control muscles, but not in muscles of the tetrodotoxin-treated rats. The observed changes in the time course of the twitch contraction with repetitive stimulation following tetrodotoxin-induced disuse are consistent with alterations in sarcoplasmic reticulum handling of calcium. It is not certain if there is a change following disuse in the mechanism normally associated with staircase or if this mechanism is merely opposed by an early fatigue.
Cardiac effects of electrically induced intrathoracic autonomic reflexes
Authors: Armour J. A.
Published: April 2011

Electrical stimulation of the afferent components in one cardiopulmonary nerve (the left vagosympathetic complex at a level immediately caudal to the origin of the left recurrent laryngeal nerve) in acutely decentralized thoracic autonomic ganglionic preparations altered cardiac chronotropism and inotropism in 17 of 44 dogs. Since these neural preparations were acutely decentralized, the effects were mediated presumably via intrathoracic autonomic reflexes. The lack of consistency of these reflexly generated cardiac responses presumably were due in part to anatomical variation of afferent axons in the afferent nerve stimulated. As stimulation of the afferent components in the same neural structure caudal to the heart (where cardiopulmonary afferent axons are not present) failed to elicit cardiac responses in any dog, it is presumed that when cardiac responses were elicited by the more cranially located stimulations, these were due to activation of afferent axons arising from the heart and (or) lungs. When cardiac responses were elicited, intramyocardial pressures in the right ventricular conus as well as the ventral and lateral walls of the left ventricle were augmented. Either bradycardia or tachycardia was elicited. Following hexamethonium administration no responses were produced, demonstrating that nicotonic cholinergic synaptic mechanisms were involved in these intrathoracic cardiopulmonary–cardiac reflexes. In six of the animals, when atropine was administered before hexamethonium, reflexly generated responses were attenuated. The same thing occurred when morphine was administered in four animals. In contrast, in four animals following administration of phentolamine, the reflexly generated changes were enhanced. As electrical excitation of afferent axons in one cardiopulmonary nerve of an acutely decentralized preparation can alter cardiac chronotropism and (or) inotropism, it is concluded that intrathoracic autonomic neuronal mechanisms exist which can modify heart rate and contractility in the absence of influences from central nervous system neurons. Furthermore, it appears that intrathoracic cardiopulmonary–cardiac reflexes capable of modifying the heart utilize a number of different synaptic mechanisms.
Effect of dopaminergic and α-adrenergic modulation on corticotropin-releasing factor immunoreactivity in rat hypothalamus
Authors: Haas Daniel A. , George Susan R.
Published: April 2011

The potential role that dopaminergic mechanisms have in the regulation of corticotropin-releasing factor (CRF) in the hypothalamus was investigated. Adult male rats were administered bromocriptine, a potent dopamine agonist, for periods ranging up to 51 days. Overall, bromocriptine treatment resulted in a significant decline in CRF-like immunoreactivity (CRF-ir). The dopamine antagonist, haloperidol, was administered for similar periods and resulted in no overall significant effect, except for a transient decrease. Treatment with reserpine, known to deplete monoamines including dopamine, induced a significant decrease in CRF-ir 24 h post-treatment. The possibility that the original results were due to α-adrenergic inhibition by bromocriptine and haloperidol was studied next. α1-Stimulation by administration of methoxamine had no significant effect. α2-Stimulation by clonidine significantly reduced hypothalamic CRF-ir. Selective depletion of neurotransmitter from noradrenergic and adrenergic neurons by 6-hydroxydopamine also resulted in a significant reduction of hypothalamic CRF-ir, an effect localized entirely to the median eminence. These results show a reduction in CRF-ir subsequent to either bromocriptine administration, generalized monoamine depletion, α2-stimulation, or selective noradrenaline–adrenaline depletion. No direct dopaminergic effects could be confirmed. These data are consistent with a constant, near-maximal α1-adrenergic effect maintaining hypothalamic CRF concentrations, presumably by inhibition of CRF release from the median eminence.
Metoclopramide blocks the phenyl diguanide and 5-hydroxytryptamine induced cardiorespiratory reflexes in cats and dogs
Authors: Ravi K. , Dev N. B.
Published: April 2011

The effects of metoclopramide on the reflex cardiorespiratory responses elicited by stimulation of pulmonary J receptors by right atrial injections of phenyl diguanide (PDG), 5-hydroxytryptamine (5-HT), and capsaicin were investigated in anesthetized spontaneously breathing cats. It was observed that while metoclopramide blocked the responses to PDG and 5-HT injections, it spared the responses to capsaicin injections. Similarly, metoclopramide was without effect on the reflex responses following activation of pulmonary C-fiber receptors (J receptors) by capsaicin in dogs. Reflex cardiorespiratory responses elicited by left atrial injections of PDG and 5-HT, owing to stimulation of cardiac receptors in cats, and reflex responses following right or left atrial injections of PDG and 5-HT, owing to stimulation of aortic chemoreceptors in dogs, were also found to be blocked by metoclopramide. Afferent impulse activity recorded from aortic chemoreceptors of dogs showed that while metoclopramide depressed the excitatory effect of PDG and 5-HT on them, it did not produce any effect on their spontaneous activity and their excitation by hypoxia. The results from the reflex studies show that metoclopramide is capable of antagonizing the reflex responses following the activation of the cardiopulmonary afferents by PDG and 5-HT. Based on the effects on aortic chemoreceptor afferents, it is suggested that PDG, 5-HT, and metoclopramide may be acting upon the regenerative region of the sensory endings.
Regional differences in lipid composition and incorporation of saturated and unsaturated fatty acids into microsomal membranes of rat small intestine
Authors: Garg M. L. , Keelan M. , Wierzbicki A. , Thomson A. B. R. , Clandinin M. T.
Published: April 2011

Incorporation of [1-14C]palmitic (16:0) and [1-14C]linoleic (18:2ω6) acids into microsomal membranes of proximal (jejunum) and distal (ileum) regions of rat small intestine was investigated, and the lipid composition, including fatty acid profiles of membrane phospholipids, was determined. Jejunal microsomes contained significantly higher amounts of total phospholipids, phosphatidylcholine, and phosphatidylinositol, and lower amounts of cholesterol and sphingomyelin when compared with ileal microsomes. Jejunal microsomal phospholipids contained higher levels of stearic (18:0), 18:2ω6, and eicosapentaenoic (20:5ω3) acids followed by reduced levels of oleic (18:1ω9), arachidonic (20:4ω6), and docosahexaenoic (22:6ω3) acids when compared with those from the ileum, except for phosphatidylinositol where no significant difference between 20:4ω6 content of each site was observed. In both jejunal and ileal microsomes, incorporation of [1-14C]18:2ω6 was significantly higher than that of [1-14C]16:0. Incorporation of both [1-14C]16:0 and [1-14C]18:2ω6 was significantly higher in jejunal microsomal lipid fractions (phospholipids, diacylglycerols, triacylglycerols) when compared with the ileal microsomal fraction. These data suggest that (1) jejunal and ileal microsomal membranes differ from each other in terms of lipid composition and lipid synthesis, (2) site variations in the specificity of acyltransferases for different fatty acids exist, and (3) higher Δ9-, Δ6-, Δ5-, and Δ4-desaturase activities exist in ileal compared with jejunal enterocytes.
Excitatory responses of trigeminal neurons to substance P suggest involvement in sensory transmission
Authors: Spigelman I. , Puil E.
Published: April 2011

Responses to substance P application were studied with intracellular recording techniques in in vitro preparations of trigeminal root ganglion neurons of guinea pigs. Perfusion of substance P in micromolar concentrations markedly depolarized neurons and reduced their input conductances. Also, the threshold for spikes evoked by injections of depolarizing current pulses was decreased. Single electrode voltage-clamp recordings showed that substance P increased inward, and decreased outward currents evoked by hyperpolarizing voltage steps from holding potentials near rest. Depolarizing responses to substance P were attenuated in Na+-deficient solutions. The excitatory actions of this endogenous peptide on the perikarya of primary sensory neurons give rise to the possibility of physiological actions of substance P at multiple sites in the trigeminal system.
Noradrenaline induces short and long duration potentiation of glutamate excitations of cultured Purkinje neurons
Authors: Marshall Kenneth C. , Tsai Willis H.
Published: April 2011

The effects of iontophoretic application of noradrenaline on spontaneous or glutamate-evoked activity were studied in Purkinje neurons in explant cultures. The most frequently observed effect of noradrenaline was a depression of glutamate responses, and this was sometimes observed in the absence of apparent changes in spontaneous activity. In 30 out of 80 cells, glutamate responses were increased during or following noradrenaline application. In 21 of the 30 cells, these potentiations were of relatively short duration (<4 min), while in the other 9, the potentiations had a much longer duration. β-Adrenergic antagonists blocked the long duration potentiations in four out of five cells, while short duration potentiation was blocked in only one of eight cells. The α-adrenergic antagonist prazosin blocked the short duration potentiations in six of eight cells. The results indicate that long duration potentiations by noradrenaline as reported in the hippocampus are also observable in the cerebellum, and that short and long duration potentiations of glutamate responses may be pharmacologically distinct.
Growth hormone depresses ethylmorphine demethylase activity: correlation with decreased levels of fast-turnover cytochrome P-450 in hypophysectomized female rats
Authors: Vockentanz Birgit M. , Virgo Bruce B.
Published: April 2011

The hepatic monooxygenase system was studied in hypophysectomized female rats infused for 5 days with ovine growth hormone (GH). At 7.5 μg∙h−1 GH decreased the total cytochrome P-450 by 16%; at 10 μg∙h−1 it reduced both cytochrome P-450 (31%) and the activity of ethylmorphine demethylase (31%). GH did not alter the activities of NADPH cytochrome c reductase or aniline hydroxylase. The lower GH dose decreased the amount of fast- and slow-turnover P-450 by 11 and 38%, respectively, while the higher dose decreased both by 49%. The loss of demethylase activity therefore correlates with the loss of fast-tumover P-450. This component is relatively more abundant in the female (fast: slow turnover of 4.3) than the male (fast: slow turnover of 2.5). GH did not affect the half-lives of the P-450 components, suggesting that it decreases their synthesis. The P-450 concentration in microsomes from GH-treated animals did not increase after incubation with hemin, suggesting that in vivo the hormone does not lower P-450 synthesis via depression of heme. Puromycin mimicked the effect of GH and when given with the hormone their effects on the P-450 levels were multiplicative (p < 0.05), suggesting different modes of action and that GH does not decrease P-450 by acting at translation.
Role of vagal and sympathetic afferents in reflex respiratory responses to capsaicin in dogs
Authors: Ravi K.
Published: April 2011

The respiratory responses following stimulation of type J (pulmonary C fiber) receptors by right atrial injections of capsaicin were assessed in spontaneously breathing anesthetized dogs. At the reflexly effective threshold dose, the primary respiratory response elicited was tachypnoea. With higher doses of capsaicin, the tachypnoea was replaced by apnoea. Left atrial injections of capsaicin also resulted in apnoea, which was abolished or reduced by injecting Xylocaine into the pericardial sac, and after vagotomy, apnoea was replaced by tachypnoea. The latter findings suggested that the apnoea produced by left atrial injection of capsaicin might be due to stimulation of receptors with vagal afferents coursing through the pericardium. In vagotomized dogs, administration of capsaicin into the abdominal aorta above the origin of the iliac arteries (the iliac arteries were kept occluded) resulted in a hyperpnoeic response. Following the transection of the spinal cord between L4 and L5, capsaicin injection into the abdominal aorta caused apnoea instead of hyperpnoea. The apnoeic response elicited was abolished by transecting the spinal cord between L1 and L2. It is suggested that the respiratory responses observed were due to stimulation of receptors in the splanchnic bed connected to sympathetic afferents.
Effect of calcium ionophore A23187 on pregnenolone metabolism to progesterone in rat granulosa cells
Authors: Tsang Benjamin K. , Mattice David F. , Li Ming , Asem Elikplimi K.
Published: April 2011

The effect of calcium ionophore A23187 on the metabolism of pregnenolone to progesterone was examined in rat granulosa cells during a 24-h culture period. Granulosa cells harvested from pregnant mare's serum gonadotropin treated immature rats were incubated in the presence and absence of the divalent cation ionophore A23187. The ionophore induced progesterone synthesis from both endogenous sterol substrate and exogenous pregnenolone in a time- and concentration-dependent manner. Pregnenolone metabolism was examined in the presence of aminoglutethimide phosphate, an inhibitor of endogenous pregnenolone production. Steroid secretion resulting from metabolism of endogenous substrate was more sensitive to A23187 in that a lower concentration of the ionophore was required to induce a significant increase than that noted for exogenous pregnenolone metabolism. In addition, progesterone production from endogenous sterol occurred 6 h earlier than the observed increase in the conversion of pregnenolone to progesterone. These results indicate that A23187 and therefore possibly enhanced calcium influx may play a significant role in the regulation of pregnenolone metabolism in granulosa cells depending on the duration of incubation. The earlier steroidogenic response from endogenous substrate may be a reflection of an acute effect of A23187 on certain steroidogenic steps proximal to pregnenolone production.
Leukotriene C4 action and metabolism in the isolated perfused bullfrog heart
Authors: Herman R. Peter , Heller R. Scott , Canavan Christopher M. , Herman Ceil A.
Published: April 2011

The effects of leukotrienes (LTs) have been widely studied in the isolated perfused mammalian heart; however, little is known about the effect or metabolism of LTs in the isolated bullfrog heart. Isolated perfused bullfrog hearts were administered randomized doses of LTC4, LTD4, or LTE4. The cardiac parameters of heart rate, developed tension, and its first derivative (dT/dt) were recorded. LTC4 was the most potent of the leukotrienes tested in eliciting positive inotropic effects. LTD4 and LTE4 were equally effective but about one order of magnitude less potent than LTC4. None of the LTs showed any chronotropic effects in this preparation. A series of [3H]LTC4 metabolism experiments were carried out using whole perfused hearts and minced bullfrog heart tissue. Isolated perfused bullfrog hearts administered [3H]LTC4 converted significant amounts to [3H]LTD4, and to a lesser degree, [3H]LTE4, during the 6-min course of collection. Both minced atrial and ventricular tissue converted [3H]LTC4 to radioactive metabolites that co-migrated with authentic LTD4 and LTE4 standards. In both tissues, the major product was [3H]LTD4, with smaller amounts of [3H]LTE4 produced. The atrium converted significantly more [3H]LTC4 to its metabolites than did the ventricle. The metabolism of [3H]LTC4 to [3H]LTD4 by both tissues was virtually abolished in the presence of serine borate. Cysteine had no effect on [3H]LTE4 production. The data in this study demonstrate that leukotrienes have the opposite inotropic effect on the heart when compared with mammals. Also in contrast to mammals, frogs metabolize LTC4 to a less potent compound and may use the LTC4 to LTD4 conversion as a mechanism of LTC4 inactivation.
Dietary effects of ω3-fatty acids on intestinal transport function
Authors: Thomson A. B. R. , Keelan M. , Garg M. , Clandinin M. T.
Published: April 2011

Animals were fed for 2 weeks on one of four isocaloric and isocholesterolic semisynthetic diets: high 18:3ω3, low 18:3ω3, high 20:5ω3, or low 20:5ω3. The weight of the intestine and the percentage of the wall consisting of mucosa was greater in high 20:5ω3 than in high 18:3ω3, and greater in low 20:5ω3 than in low 18:3ω3, although the mucosal surface area was 26% lower in high 20:5ω3 than high 18:3ω3. The jejunal uptake of 40 mM glucose and ileal uptake of 40 mM galactose was greater in high 18:3ω3 than in high 20:5ω3; jejunal uptake of fatty acid 12:0 was higher, but 18:0 was lower in high 18:3ω3 than in high 20:5ω3. The jejunal or ileal uptake of cholesterol was not affected by 20:5ω3. However, 20:5ω3 had a variable effect on the uptake of medium- and long-chain fatty acids. Alterations in the uptake of fatty acids and glucose were not explained by any difference in the animals' food consumption, body weight gain, or intestinal weight, but the reduced jejunal uptake of 40 mM glucose in rats fed the high 20:5ω3 diet was associated with reduced mucosal surface area. Thus, (i) varying the source of ω3-fatty acids (vegetable, 18:3ω3 versus fish oil, 20:5ω3) altered the mucosal mass of the intestine, and (ii) the source of the dietary ω3-fatty acid (18:3ω3 versus 20:5ω3) influenced intestinal hexose uptake, with fish oil having an anti-absorptive effect on the jejunal uptake of D-glucose.
Relationship between dietary tyrosine and plasma cholesterol in the rat
Authors: Jacques Hélène , Deshaies Yves , Savoie Laurent
Published: April 2011

The present study was undertaken to measure the effects of dietary tyrosine added to fish protein and peanut meal on plasma cholesterol and plasma thyroid hormone levels in the rat. These dietary proteins were chosen because they contain similar amounts of tyrosine but release it at different rates during enzymatic hydrolysis. Casein was chosen as the reference protein. Supplementation was used to obtain tyrosine levels similar to that of casein. Male Sprague–Dawley rats were fed cholesterol-enriched diets containing 15% protein. After 3 weeks of experimental feeding, total postprandial plasma cholesterol was similar in the casein and peanut meal groups and significantly lower in the fish group. When added to the fish diet, tyrosine caused an increase in plasma cholesterol to a level similar to that of the casein group, whereas supplementation had no effect on plasma cholesterol of rats fed the peanut meal diet. The effects of dietary proteins or of tyrosine supplementation on cholesterol levels of the (density < 1.006 g/mL) lipoprotein fraction were comparable, but not all significant, to those observed on total plasma cholesterol. In addition, casein and fish diets induced significantly higher levels of plasma triiodothyronine (T3) and lower levels of plasma thyroxine (T4) than did the peanut meal diet. However, the addition of tyrosine to the fish or the peanut meal diet did not modify the plasma thyroid hormone levels. These results showed that tyrosine supplementation in a physiological amount may increase cholesterol levels in the rat when added to protein, with a slow release of tyrosine during digestion, and that the tyrosine effect was not related to the plasma thyroid hormone levels.
Potassium, sodium, water, and Donnan potential changes in the myofibrils of intact muscle fibres after exposure to ouabain and K-free Ringer
Authors: Fong C. N. , Hinke J. A. M.
Published: April 2011

Frog sartorius muscles were superfused for 40 min with solutions of K-free Ringer, normal Ringer containing ouabain, or K-free Ringer containing ouabain. Changes in myoplasmic K and Na were measured with ion-selective microelectrodes; changes in total fibre K and Na were measured by means of atomic absorption spectroscopy; and changes in total fibre water content were obtained from wet and dry weights. Application of a two-compartment model permitted one to calculate (i) the K, Na, and water changes in the myofibrils and in the surrounding myoplasm (extramyofibrillar space); (ii) the changes in the transmyofibrillar Donnan potential (ED); and (iii) the changes in the ratio of the apparent association constants (kNa/kK) of the myofilament charge sites to Na and K. In the resting fibres, the K, Na, and water content of the myofibrils were calculated to be 82, 87, and 80% of total fibre content, respectively; ED was calculated as −4.5 mV; kNa/kK was calculated as 1.4. After a 40-min ouabain treatment, 12 mmol (per kg fibre water) of intrafibre K exchanged with 7.5 mmol of extrafibre Na, 6.4 mmol of myofibrillar K exchanged with an equal amount of extramyofibrillar Na, ED increased to −8.3 mV, and kNa/kK remained relatively constant. After a 40-min K-free treatment, the fibres gained 5.5 mmol of Na without any change in fibre K or water, the myofibrils shifted 9.3% of their water into the extramyofibrillar space instead of exchanging K for Na, ED increased to −10.7 mV, and kNa/kK decreased to 0.47. When ouabain and zero K were combined, an equimolar transmembrane K for Na exchange occurred, the myofibrils appeared to shift water and to exchange K for Na, ED increased to −14.3 mV, and kNa/kK decreased to 0.63. Analyses of other experiments involving Na-free superfusions suggest that the zero K-induced intrafibre water shift is dependent on an uncompensated net accumulation of Na in the extramyofibrillar myoplasm. These results indicate that the myofibrils in the intact fibre may adjust their water and electrolyte content quite differently during different perturbations, and that the myofibrillar changes need not mimic the whole fibre water and electrolyte changes.
Hindlimb skeletal muscle blood flow during sympathetic nerve block before and during acute anemia
Authors: Kubes P. , Cain S. M. , Chapler C. K.
Published: April 2011

The role of sympathetic innervation in the regulation of hindlimb skeletal muscle blood flow (QL) and metabolism was studied prior to and during acute anemia in anesthetized, paralyzed, and ventilated dogs (n = 8). Neural activity in the sciatic nerve was reversibly cold blocked for a 15-min period at control hematocrit (Hct., 51%) and again at 30 min of anemia (Hct., 14%). At the end of each experiment the sciatic nerve was transected and maximally stimulated (frequency, 10 Hz; duration, 2.0 ms). Arterial blood pressure and [Formula: see text] were measured continuously; skeletal muscle vascular hindrance (ZL) and oxygen uptake [Formula: see text] were calculated. When the sciatic nerve was cold blocked prior to and during anemia, ZL decreased to the same absolute value and [Formula: see text] remained unchanged. Prior to anemia the mean [Formula: see text] increased (p < 0.05) from 99 to a peak value of 165 mL∙kg−1∙min−1 during cold block; [Formula: see text] had returned to control by 10 min of cooling. During anemia, [Formula: see text] increased (p < 0.05) from 160 to 307 mL∙kg−1∙min−1 during sympathetic cold block, while maximal sympathetic stimulation decreased [Formula: see text] to 87 mL∙kg−1∙min−1. [Formula: see text] remained above (p < 0.05) the anemia control value (160 mL∙kg−1∙min−1) at 10 min of cooling. Hindrance increased from 0.30 to 0.38 peripheral resistance units/centipoise following the induction of anemia and this was shown to be sympathetically mediated because hindrance was decreased to the same level during cold block prior to and during anemia.
Splenic immune responses following treadmill exercise in mice
Authors: Hoffman-Goetz L. , Thorne R. J. , Houston M. E.
Published: April 2011

The in vitro proliferation response to lipopolysaccharide and pokeweed mitogen by splenic lymphocytes and the effect on the total splenic lymphocyte number were examined in C57BL/6J mice following an 8-week treadmill training program (30 m/min, 8° slope, 30 min/day, 5 times/week) and after a single bout of exhaustive exercise (50% stepwise increases in final running speed for 10-min intervals). Plasma corticosterone levels were also measured to evaluate whether changes in adrenocortical activation were associated with exercise-induced immunomodulation. In comparison to sedentary controls, trained mice had an increase of 35% in succinate dehydrogenase activity per unit of protein in the quadriceps femoris muscle. Trained mice showed an increase in splenic lymphocyte proliferation to both mitogens which was evident 72 h after completion of the final training session, relative to sedentary controls. Immediately following exercise, however, lymphocyte proliferative responses were depressed compared with the training and the control values. The exercise regimen resulted in a reduction in total number of mononuclear cells per spleen. Changes in plasma corticosterone levels after exercise were not clearly associated with immunodepression or immunoenhancement of splenic lymphocyte mitogenesis. Taken together, the data suggest that moderate endurance training augments splenic B lymphocyte mitogenesis and further, that the immediate effects of exercise on splenic immune function vary with the duration and intensity of the work.
Digitalis-like pregnanes. Cardiac and renal effects of a glycoside of 14β-hydroxyprogesterone
Authors: Templeton J. F. , Kumar V. P. Sashi , Bose D. , Smyth D. D. , Kim R. S. , LaBella F. S.
Published: April 2011

The synthesis of the glucoside, 3β-[(β-D-glucopyranosyl)oxy]-14-hydroxy-14β-pregn-4-en-20-one, a 14β-hydroxyprogesterone glucoside (14β-OHP-glu), is described. This compound has an IC50 of 1 μM in a [3H]ouabain binding assay, and is about 10 times more potent than the aglycone. Like 14β-hydroxyprogesterone, the glucoside enhances contractility of isolated cardiac muscle. 14β-OHP-glu or ouabain, when infused at comparable doses into the renal artery of the anesthetized rat, markedly increases urine volume. Whereas ouabain significantly enhances urinary potassium excretion with little or no effect on sodium excretion, 14β-OHP-glu promotes a marked natriuresis with no significant effect on potassium excretion.
Effets du chlorhydrate d'heptaminol sur la transmission neuromusculaire
Authors: Vautrin Jean , Mambrini Jean , Mauro Nicole , Quillent Caroline
Published: April 2011

6-Amino-2-methyl-2-heptanol chlorhydrate, heptaminol chlorhydrate, blocks the response to indirect stimulation of the mouse diaphragm in vitro. This effect is due to a dose-dependent pre- and post-synaptic block of neuromuscular transmission starting at 1 mM heptaminol (HEPT). The complete block of neuromuscular transmission occurs at 10 mM. At 2 mM, the decrease in quantal size is more significant in the presence of d-tubocurarine than when the extracellular calcium is lowered. At this concentration, heptaminol also prolongs the depolarization time of the motor end plate potential. Slightly higher concentrations of heptaminol produce a decrease in quantal content. This latter effect is associated with an increase in synaptic delay.
Differential cardiovascular effects of central clonidine and B-HT 920 in conscious rats
Authors: King Kathryn A. , Pang Catherine C. Y.
Published: April 2011

The effect of intracerebroventricular (i.c.v.) injection of the α2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 μg clonidine significantly decreased MAP and slightly decreased HR. Plasma noradrenaline and adrenaline levels were slightly but not significantly decreased after the injection of 1 μg clonidine. In contrast, the injection of 0.1–10.0 μg B-HT 920 increased MAP and decreased HR. Plasma noradrenaline and adrenaline levels were slightly increased after the injection of the 1- and 10-μg doses. The i.c. v. injection of the α2-antagonist rauwolscine slightly but not significantly increased MAP and plasma noradrenaline and adrenaline levels. The responses to i.c. v. injection of clonidine and B-HT 920 were not changed by prior administration of rauwolscine. Neither the pressor response to B-HT 920 nor the depressor response to clonidine was abolished by rauwolscine, suggesting that neither response was mediated by α2-adrenoceptors.
Role of cGMP in relaxation of vascular and other smooth muscle
Authors: Nakatsu Kanji , Diamond Jack
Published: April 2011

The hypothesis that the relaxant action of many drugs on vascular and other smooth muscle is mediated by increases in intracellular cGMP, the "cGMP hypothesis," is gaining wide acceptance. While much information supporting this idea can be found in the literature, there is also a significant amount of information indicating that an elevation in the tissue content of cGMP is by itself insufficient to cause smooth muscle relaxation. The literature is reviewed with reference to the criteria that need to be fulfilled to consider cGMP as the second messenger mediating relaxation of smooth muscle by a drug; i.e., activation of guanylate cyclase, elevation of tissue content of cGMP, potentiation by phosphodiesterase inhibitors, antagonism by inhibitors of cGMP synthesis, and production of relaxation by cGMP analogues. For each criterion, key observations supporting the hypothesis are considered, followed by examples of important observations not consistent with the hypothesis. It is concluded that in some smooth muscles, for example, rat myometrium and vas deferens, cGMP is not a mediator of drug-induced relaxation. In other smooth muscles, including vascular smooth muscle, cGMP appears to play an important role in the relaxation process; but current evidence suggests that other factors are also important and that the cGMP hypothesis may need to be modified.Key words: cGMP, vascular relaxation, smooth muscle relaxation, vasodilators.
Effects of manganese chloride, verapamil, and hypoxia on the rate-dependent increase in internal longitudinal resistance of rabbit myocardium
Authors: Alvarez Julio , Rousseau Georgina , Dorticós Francisco , Morlans Jesús
Published: April 2011

The effects of high rates of stimulation on the internal longitudinal restivity (Ri) and conduction velocity (θ) were studied on rabbit papillary muscle preparations using a silicon-oil chamber. Increasing the rate from 75 to 150/min caused Ri to rise and θ to decrease. The maximum rate of depolarization and action potential duration were also decreased. At a rate of 300/min the effects were more pronounced. Blockade of the slow inward current (Isi) and of the Na–Ca exchange by MnCl2 (5 mmol/L) did not prevent rate-induced changes in these variables. Verapamil (0.02 mmol/L) was also ineffective. Hypoxia [Formula: see text] at 75/min induced changes in Ri and θ which were similar to those recorded at 150/min under aerobic conditions. The effects of high rates of stimulation were potentiated under hypoxia. From the present results it is suggested that Isi and the Na–Ca exchange are not the main determinants of the rate-induced increase in Ri, which could be determined by other intracellular Ca-release mechanisms or by a decrease in myoplasmic pH.Key words: intercellular coupling, conduction velocity, calcium channel blockers.
Characterization of the muscarinic and serotoninergic receptors of the intestine of the rainbow trout (Salmo gairdneri)
Authors: Burka John F. , Blair Rosalind M. J. , Hogan Jane E.
Published: April 2011

The ability of carbachol and 5-hydroxytryptamine (5-HT) to contract isolated segments of rainbow trout intestine in a concentration-dependent manner indicates the presence of muscarinic and serotoninergic receptors in this tissue. The activity of these agonists appears to be directly on the smooth muscle, since ganglionic blockers and inhibitors of neurotransmission did not inhibit contractions. The carbachol-induced contractions were selectively inhibited by atropine and (±)-3-quinuclidinyl xanthene-9-carboxylate hemioxalate hydrate, an M-2 muscarinic receptor antagonist. However, the inhibition was not competitive. McN-A-343, an M-1 muscarinic agonist had no effect on intrinsic tone. The 5-HT-induced contractions were selectively inhibited by methysergide and the 5-HT2 receptor blockers, ketanserin and 1-(1-naphthyl)piperazine. Again, the inhibition by these agents was not competitive. 5-HT1 and 5-HT3 receptor antagonists did not inhibit contractions. The results thus suggest that the smooth muscle of the rainbow trout intestine contains M-2 muscarinic and 5-HT2 receptors.Key words: smooth muscle, gastrointestinal tract, trout, muscarinic receptors, serotonin.
Acetylcholine inhibition in rabbit sinoatrial node is prevented by pertussis toxin
Authors: Molyvdas Paschalis-Adam , Sperelakis Nick
Published: April 2011

The effects of acetylcholine (ACh) were examined on the naturally occurring slow action potentials (APs) of the isolated, organ-cultured, spontaneously beating sinoatrial (SA) node of the rabbit, in the presence or absence of pertussis toxin. The sensitivity of the SA-node preparations to ACh was not altered after 24 h incubation in organ culture medium. Activation of the muscarinic receptor hyperpolarized the cells and reduced the frequency of spontaneous activity at low concentrations (1 × 10−6 and 3 × 10−6 M), and completely abolished automaticity at higher concentrations (1 × 10−5 M). However, stimulated activity was maintained. Increased concentrations (1 × 10−4 M) of ACh completely abolished excitability. When the SA-node preparations were cultured in the presence of 0.5 μg/mL pertussis toxin, concentrations of ACh as high as 1 × 10−4 M had no effect on the AP parameters and frequency of spontaneous activity. The results indicate that inactivation of G proteins by pertussis toxin caused inhibition of the ACh effects on the automaticity of the SA node. In addition, the blocking effect of ACh to the naturally occurring slow APs was also inhibited by pertussis toxin. We conclude that in the rabbit SA node, the effects of ACh on automaticity and on the slow channels are mediated by G protein.Key words: sinoatrial node, acetylcholine, pertussis toxin.