bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergism between ouabain and monensin in neurogenic responses of guinea-pig vas deferens
Authors: Katsuragi Takeshi , Kuratomi Lulu , Miyamoto Koji , Furukawa Tatsuo
Published: April 2011

Interrelations between ouabain, a Na+–K+ ATPase inhibitor, and monensin, a Na+ ionophore, on noradrenaline liberation and contractile activity were evaluated in the guinea-pig vas deferens. Monensin (1 μM) per se elicited a small contraction of the tissue. However, amplitude and time to the peak of large and sustained contractions evoked by 10 μM ouabain were potentiated and markedly shortened, respectively, by monensin. Contractions elicited by ouabain with or without monensin were prevented by 3 μM phentolamine or by pretreatment with reserpine. Contractions evoked by K+-free solution were augmented by monensin. In an HPLC study, noradrenaline outflow from the vas deferens was moderately and considerably increased by monensin (10 μM) and ouabain (100 μM), respectively. The ouabain-evoked output of noradrenaline was enhanced in the presence of monensin and the time course for maximum noradrenaline release was shortened, as was the contractile activity. This enhanced outflow after ouabain plus monensin was reserpine sensitive but not tetrodotoxin sensitive. Furthermore, this noradrenaline outflow was roughly halved in Na+-deficient medium, but was unaltered in Ca2+-free medium. These findings suggest that the synergistic effect of ouabain and monensin on noradrenaline liberation from the guinea-pig vas deferens may be due to an elevation of cytoplasmic Ca2+ concentrations, presumably resulting from a stimulation of intracellular Na+–Ca2+ exchange system, but not enhanced Ca2+ entry.
Existence of two types of postjunctional α-adrenoceptors in the isolated canine internal carotid artery
Authors: Kawai Yasuaki , Kobayashi Shigeaki , Ohhashi Toshio
Published: April 2011

The pharmacological characteristics of postjunctional α-adrenoceptors in isolated canine internal carotid arteries were investigated by the use of selective agonists and antagonists for α1 and α2-adrenoceptors. Norepinephrine, phenylephrine, and xylazine caused concentration-dependent contractions in the helical strips. The contraction induced by 10−4 M xylazine was significantly smaller than that produced by 10−4 M norepinephrine or 10−4 M phenylephrine. The contraction induced by 10−4 M phenylephrine was almost the same value as that induced by 10−4 M norepinephrine. Phentolamine (10−8 and 10−7 M) caused a parallel shift to the right of the concentration–response curve to norepinephrine. The contractile responses to low concentrations of norepinephrine were significantly suppressed by pretreatment with an α2-antagonist such as yohimbine (10−9 and 10−8 M) or DG 5128(10−7 and 10−6 M). On the other hand, the responses to higher concentrations of norepinephrine were mainly reduced by low concentrations of an α1-antagonist, prazosin (3 × 10−10 and 3 × 10−9 M). These results suggest that both α1- and α2-adrenoceptors are located on the plasma membrane of smooth muscle cells in canine internal carotid arteries and that the norepinephrine-induced contractions at low and high concentrations are mainly mediated by activation of α2- and α1-adrenoceptors, respectively.
Effect of nickel chloride on streptozotocin-induced diabetes in rats
Authors: Novelli Ethel L. B. , Rodrigues Ney L. , Ribas Bartolomé O.
Published: April 2011

The potential of nickel chloride to prevent streptozotocin-induced hyperglycemia was tested in rats in vivo. To induce diabetes, streptozotocin (100 mg/kg body weight) was injected as a single dose. Streptozotocin treatment resulted in a significant decrease in plasma insulin and ceruloplasmin, and pancreatic Cu, protein, and Cu–Zn superoxide dismutase activity. In rats treated with nickel chloride (10 mg/kg body weight) and streptozotocin, these values were comparable with those observed in control rats. The results indicate that nickel chloride injected before streptozotocin prevented streptozotocin-induced hyperglycemia, and suggest that the protective effect was related to Cu–Zn superoxide dismutase activity, mediated by copper.
Comparative hemostatic protein alterations accompanying pregnancy and parturition
Authors: Gentry P. A. , Liptrap R. M.
Published: April 2011

Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationship of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced. Results from injection of various steroid hormones in the dog, pig, and rabbit have shown this to also hold true for these species. In both the dog and the pig, progesterone and the prostaglandin, PGF2α, induce marked increases in fibrinogen values, while estrogen alone has apparently no effect on this protein. These results emphasize the lack of a clear understanding of the relationship between the coagulation proteins and reproductive hormone changes. In all species examined, fibrinogen values rise at parturition when progesterone values are falling. Although in the human female the effect of pregnancy and ingestion of oral contraceptives on fibrinolysis has been examined, this aspect of the hemostatic process has not been evaluated in domestic animals. The paucity of information and the diversity of the response of the coagulation proteins in different species to hormonal manipulation reflect the limited understanding that exists pertaining to the interrelationships between circulating hormones, coagulation proteins, and hemostasis.
Bile protein secretion in the rat stimulated by taurocholate effect of chloroquine
Authors: Marinelli R. A. , Carnovale C. E. , Garay E. A. Rodríguez
Published: April 2011

The biliary protein excretion during sodium taurocholate induced choleresis was studied in normal rats and in rats treated with the lysosomotropic agent, chloroquine. The analysis of the protein component in bile was made on SDS–polyacrilamide gel, and the individual polypeptides were quantitated by densitometry. The excretion of bile polypeptides was compared with that of lysosomal acid phosphatase. The biliary excretion of polypeptides of molecular mass lower than and equal to 54 kDa was markedly stimulated by taurocholate-induced choleresis. Chloroquine treatment of rats diminished the biliary excretion of such polypeptides and also inhibited their excretion induced by taurocholate. The behaviour of these polypeptides was well correlated to that of the lysosomal marker. The biliary excretion of polypeptide bands of a higher molecular mass (up to 140 kDa) did not show major changes during taurocholate-induced choleresis in any of the groups. The results indicate that biliary excretion of proteins in the rat may be either stimulated by taurocholate or may be independent of the bile salt. The former requires the functional integrity of chloroquine-sensitive hepatocyte compartments, which may involve the lysosomes.
Leukotriene and anti-IgE induced contractions of human isolated trachea: studies with leukotriene receptor antagonists and a novel 5-lipoxygenase inhibitor
Authors: Jones Thomas R. , Charette Luc , Denis Danielle
Published: April 2011

The pharmacological actions of three leukotriene D4 (LTD4) receptor antagonists, FPL-55712, L-648,051, and L-649,923, and a novel inhibitor of leukotriene biosynthesis, L-651,896, have been investigated on isolated human tracheal smooth muscle. In the order of potency L-648,051 > FPL-55712 > L-649,923, these agents antagonized contractions to LTD4 and produced parallel rightward shifts in the dose–response curves. Mean −log KB values against LTD4 were 6.9 ± 0.1, 6.5 ± 0.3, and 6.0 ± 0.1 for L-648,051, FPL-55712, and L-649,923, respectively. FPL-55712 also antagonized contractions to LTC4 (−log KB value, 6.4 ± 0.3) and this activity was not decreased by the γ-glutamyl transpeptidase inhibitor, L-serine borate. In the presence of 1 × 10−7 M atropine, 7 × 10−6 M mepyramine, and 1.4 × 10−6 M indomethacin, L-648,051 at 2 × 10−5 and 2 × 10−6 M produced complete and partial blockade, respectively, of the contraction to goat anti-IgE. L-649,923 and FPL-55712 produced partial but significant inhibition at 2 × 10−5 M, whereas the 5-lipoxygenase inhibitor, L-651,896, produced almost complete inhibition at 3.5 and 35 × 10−6 M. L-Serine borate (15 mM) did not alter the activity of FPL-55712 versus anti-IgE. These findings indicate that LTD4 receptors mediate contraction of human trachea to exogenously applied and endogenously (anti-IgE) released leukotrienes. LTD4 antagonists, such as L-648,051, may be useful in assessing the role of leukotrienes in respiratory disease.
Cyclooxygenase products formed by primary cultures of cells from human chorion laeve: influence of steroids
Authors: Gibb W. , Riopel L. , Collu R. , Ducharme J. R. , Mitchell M. D. , Lavoie J. C.
Published: April 2011

Cells were isolated from human chorion laeve obtained at term (38–40 weeks gestation) by elective caesarean section and were maintained in primary culture for 1 week in defined media supplemented with 10% fetal calf serum. The production of various cyclooxygenase products by the cultures was examined. Little or no prostaglandin (PG) F2α, 6-keto-PGF1α, thromboxane B2, or 13,14-dihydro-15-keto-PGF2α was found. In contrast, the cells produced PGE2 which was low on day 0, increased during culture to a maximum on day 1 or 2, then declined to low levels. When cells were grown in the presence of media containing cortisol, dexamethasone, progesterone, and estradiol (at 10−7 or 10−9 M), the glucocorticoids (at 10−7 and 10−9 M), but not estrogen or progesterone, markedly inhibited the increase in PGE2 output. There was no difference in the protein content and thymidine incorporation of cells grown in the presence of glucocorticoids when compared with controls. This inhibitory effect was not sensitive to cycloheximide (1 μg/mL) indicating protein synthesis may not be involved in the process. These studies indicate that PGE2 is the major prostaglandin formed by primary cultures of chorion laeve and that prostaglandin metabolism in the chorion is sensitive to glucocorticoid inhibition.
Dual role of norepinephrine in the hippocampal CA1 region of the rat: inhibition and disinhibition
Authors: Leung Patrick P.-H. , Miller James J.
Published: April 2011

Norepinephrine (NE) has been shown to produce either an inhibitory or an excitatory influence on CA1 pyramidal neurons of the hippocampus depending on the dosage. It was suggested that NE, in addition to exerting a direct inhibitory effect on pyramidal cells, may also act upon recurrent inhibitory interneurons to produce a disinhibition of the pyramidal cells. The present study was undertaken to examine the effect of NE on alveus-evoked inhibition, presumably mediated by the basket cell interneurons innervating the pyramidal cells. Experiments were carried out on the in vitro hippocampal slice preparation and inhibition was assessed by the percent reduction of the stratum radiatum evoked population spike response when preceded by a conditioning pulse delivered to the alveus to activate the inhibitory interneurons via the recurrent collaterals of the pyramidal cells. Paired pulse stimulation resulted in inhibition of the stratum radiatum evoked test response with conditioning-test intervals up to 60 ms. NE (50 μM) perfusion resulted in a significant and reversible reduction of the alveus-evoked recurrent inhibition. Intracellular recordings using a similar paired pulse paradigm corroborated the extracellular data well. The possible roles of NE in the physiological functioning and pathophysiology of epileptiform activity of the hippocampus are discussed.
Intramuscular substrate depletion and fatigability of soleus grafts in rats
Authors: Côté Claude , White Timothy P. , Faulkner John A.
Published: April 2011

We investigated the relationship between oxidative capacity, substrate depletion, and fatigability of muscle grafts in situ. Isometric contractile properties and fatigability were measured in stabilized grafts and control muscles from age-matched rats. Intramuscular glycogen and triglyceride concentrations were measured before and after the fatigue protocol. Even though stabilized soleus grafts have a reduced oxidative capacity compared with control soleus muscles, no difference was observed between groups in terms of resistance to fatigue. Glycogen concentrations did not decrease significantly during the fatigue protocol in either group. Compared with control muscles, the triglyceride concentration in the grafts was significantly higher before the fatigue protocol and it decreased significantly more following the fatigue protocol.
The effects of axotomy on electrophysiological properties of B cells of bullfrog sympathetic ganglia conditioned by a previous lesion
Authors: Kelly M. E. M. , Bisby M. A. , Lukowiak K.
Published: April 2011

In bullfrog sympathetic B cells, axotomy decreases the amplitude and decay time of membrane afterhyperpolarization (AHP) and increases action potential (AP) duration. A second (test) axotomy, 7 days after an initial (conditioning) axotomy, did not amplify these changes. No recovery of AHP amplitude or AP duration occurred by 56 days post-axotomy, but AHP decay time recovered 21 days earlier than after test axotomy alone. Conditioning, previously shown to accelerate regeneration, speeds the return to normal of those membrane properties previously shown to recover after axotomy.
Binding of [3H]befunolol to β-adrenoceptors in cardiac muscles of fetal and neonatal rat
Authors: Koike Katsuo , Tanaka Hikaru , Shigenobu Koki , Takayanagi Issei
Published: April 2011

Characterization of β-adrenoceptors was studied in heart muscles of rat fetus and neonate. The results of binding assay with [3H]befunolol, a β-adrenergic partial agonist, to membrane fractions from rat heart muscles indicate that β-adrenoceptors contain two different affinity sites. In the presence of 5′-guanylylimidodiphosphate, the low affinity site was reduced, while the high affinity site was not affected. The dissociation constants for both sites did not change during pre- and post-natal development. But the maximum binding sites for both sites decreased slightly but significantly (p < 0.05) during development. A 10-fold decrease in norepinephrine sensitivity and isoprenaline sensitivity during pre- and post-natal development was not explained by the slight decrease in the maximum binding sites.
Slow cardioacceleration mediated by noncholinergic transmission in the stellate ganglion of the cat
Authors: Bachoo Manjit , Isacoff Ehud , Polosa Canio
Published: April 2011

In C1-spinal, pentobarbital-anaesthetized or anemically decerebrated cats, the preganglionic input to the acutely decentralized right stellate ganglion was stimulated with 10- to 30-s trains at 20–40 Hz. Electrical stimulation consistently produced an increase in heart rate in the presence of blocking doses of hexamethonium and atropine or after depletion of acetylcholine from the preganglionic axons by prolonged low frequency stimulation in the presence of hemicholinium. The increase in heart rate had a delayed slow onset, lasted several minutes, and was abolished by propranolol or by section of the inferior cardiac nerve. The magnitude and duration of the heart rate increase were related to intensity, frequency, and duration of preganglionic stimulation. The response to stimulation of a given white ramus was progressively attenuated, and eventually irreversibly lost, during prolonged continuous stimulation of that ramus, while the response to stimulation of a different unstimulated ramus was unchanged. We conclude that the slow cardioacceleration results from a slow and prolonged excitation of postganglionic neurons by a noncholinergic transmitter released by the preganglionic axons.
Contracture and cell damage in calcium paradox is not caused by lipid peroxidation
Authors: Belluk B. , Gupta M. , Singal P. K.
Published: April 2011

The role of oxygen radicals and lipid peroxidation in calcium-paradox injury in isolated perfused rat hearts was studied by examining the effects of mannitol and (or) allopurinol on this phenomenon. Myocardial changes due to calcium paradox were characterized by contractile failure, a rise in resting tension, and cell damage. These changes were also accompanied by increased lipid peroxidation, as indicated by an increase in malondialdehyde content. Mannitol (an effective quencher of hydroxyl radicals) treatment resulted in a dose-dependent decrease in lipid peroxidation but did not affect other changes due to calcium paradox. Allopurinol (an inhibitor of xanthine oxidase) neither affected lipid peroxidation nor modified any of the structure–function changes due to calcium paradox. These data demonstrate the occurrence of lipid peroxidation which, however, may not be involved in the observed structure–function changes due to calcium paradox. It is also suggested that in this experimental model, xanthine oxidase may not be the inducer of oxygen radicals or of lipid peroxidation.
Absence of increased oxygen consumption in brown adipose tissue of rats exhibiting "cafeteria" diet-induced thermogenesis
Authors: Ma Stephanie W. Y. , Foster David O. , Nadeau Brita E. , Triandafillou Joan
Published: April 2011

Young male Sprague–Dawley rats were induced to overeat (~45%) by provision of a "cafeteria" (CAF) diet of palatable human foods. Normophagic rats fed a commercial chow or a semisynthetic diet served as controls. The CAF rats exhibited (a) the reduced food efficiency and the propranolol-inhibitable elevation in resting metabolic rate (resting [Formula: see text]) that are indicative of a facultative diet-induced thermogenesis (DIT) by which excess energy gain is resisted, and (b) certain changes in brown adipose tissue (BAT) that are among those taken as evidence for BAT as the effector of DIT, e. g., increased protein content and increased mitochondrial binding of GDP. To assess directly and quantitatively the contribution by BAT to the elevation in [Formula: see text] (apparent DIT) of the CAF rats, BAT O2 consumption was determined (Fick principle) from measurements of tissue blood flow (microsphere method) and the arteriovenous difference in blood O2 across interscapular BAT (IBAT). To obtain the measurements, the animals were fitted under halothane anesthesia with vascular cannulas for intraventricular injection of microspheres and sampling of arterial blood and the venous effluent of IBAT. After recovery from anesthesia and rewarming to normal body temperature the animals were placed singly in a temperature-controlled metabolic chamber and the measurements, which also included determination of resting [Formula: see text], were made 1.5–2 h later at about 11:30 h. As determined from measurements made at 28 °C (thermoneutrality) mean values of resting [Formula: see text] for the cannulated rats were unchanged from those of intact (unoperated) CAF or control rats. At either 28 or 24 °C (housing temperature) the CAF rats, although exhibiting the elevation in resting [Formula: see text] attributed to DIT, were found to have levels of BAT O2 consumption no greater than those in the control rats. Thus, direct measurement of the metabolic rate of BAT in vivo produced no evidence for BAT as the effector of the DIT of CAF rats.
The effects of different membrane isolation and purification techniques on D-glucose transport into rat brush-border membrane vesicles
Authors: Johnston G. A. , Freeman H. J.
Published: April 2011

Current and widely used methods for the isolation and purification of brush-border membranes involve the aggregation of non-brush-border membranes with the divalent cations Ca2+ or Mg2+ with or without subsequent exposure to chaotropic agents (e.g., KSCN). Evidence suggests that these techniques yield morphologically distinct and heterogeneous populations of membranes and that functional differences exist between membrane vesicles prepared by the different procedures, presumably reflecting this heterogeneity. To investigate the effect of the various isolation techniques on the kinetic parameters of D-glucose transport, rat intestinal brush-border vesicles were prepared by each of the following four methods: (i) Ca2+ precipitation; (ii) Ca2+ precipitation with KSCN treatment; (iii) Mg2+ precipitation; and (iv) Mg2+ precipitation with KSCN treatment. Membrane purity as indicated by the enrichment of the enzyme membrane markers sucrase and alkaline phosphatase did not differ between isolation procedures. The Mg–Na–K ATPase activity showed an enrichment factor of less than 1.0 for each of the isolation techniques. D-Glucose uptake was measured with a rapid filtration method under conditions of a zero-trans, 100 mM cis-NaSCN gradient. The membrane preparations yielded similar Hofstee transformations displaying the curvilinear relationship thought to be consistent with the existence of multiple transporters for D-glucose. The average kinetic parameters calculated from the Hofstee plots for each technique were similar. It was concluded that D-glucose transport into rat jejunal membrane vesicles was unaffected by the variation in morphology arising from the technique used to purify the membranes.
Tachykinin involvement in cutaneous anaphylaxis in the guinea pig
Authors: Hamel R. , Ford-Hutchinson A. W. , Blazejczak C. , Brekel A. Van Den
Published: April 2011

Permeability changes in the guinea-pig skin following intradermal (i.d.) injection of tachykinin agonists or antigen were monitored through the extravasation of 99mTc-labelled human serum albumin and blood flow changes through the accumulation of 51Cr-labelled microspheres. A variety of synthetic and natural tachykinins, including substance P and neurokinins A and B, were shown to be potent inducers of permeability changes. Neurokinins A and B, but not substance P, were also shown to be apparent vasoconstrictor agents. Permeability responses in sensitized guinea pigs to i.d. injection of antigen and substance P, but not histamine, were abolished by pretreatment with the tachykinin antagonists [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [D-Pro2, D-Trp7,9]-substance P. Interpretation of such results was complicated by the fact that such antagonists may in themselves induce mast cell activation. Depletion of substance P containing neurons by pretreatment of guinea pigs with capsaicin also produced significant inhibition of antigen-induced permeability changes. These results indicate a possible role for tachykinins, such as substance P, in cutaneous anaphylaxis in the guinea pig.
[3H]U69,593 binding in guinea-pig brain: comparison with [3H]ethylketazocine binding at the κ-opioid sites
Authors: Tiberi Mario , Payette Paul , Mongeau Raymond , Magnan Jacques
Published: April 2011

[3H]U69,593 and [3H]ethylketazocine (μ + δ suppressed) binding was measured in homogenates of guinea-pig brain. Both ligands bind with high affinity to a single class of opioid sites. The relative equilibrium dissociation constant (KD) for [3H]U69,593 is 1.15 nM, while [3H]ethylketazocine has a KD value of 0.33 nM. Their respective maximum binding capacities are 4.49 and 4.48 pmol/g of wet tissue. Various μ-selective, δ-selective, κ-selective, and nonselective opioids were tested in competition studies against the binding of [3H]U69,593 or [3H]ethylketazocine (in the presence of μ- and δ-blockers) to measure their relative affinity. [D-Ala2, MePhe4,Gly5-ol]enkephalin (μ-selective) has low affinity (600–3000 nM) and [D-Pen2,D-Pen5]enkephalin and [D-Ser2, Leu5, Thr6]enkephalin (δ-selective) have very low affinities (> 20 000 nM) at the sites labelled with [3H]U69,593 or [3H]ethylketazocine. On the other hand, unlabelled U69,593, U50,488H, and tifluadom (all three κ-selective substances) display high affinity (1–5 nM) at those sites. Nonselective opioids, such as bremazocine, levorphanol, and ethylketazocine show similar affinities at the sites labelled with [3H]U69,593 and at the sites labelled with [3H]ethylketazocine. These data indicate that [3H]U69,593 is a selective high-affinity ligand for the same sites that are labelled with [3H]ethylketazocine (in the presence of μ- and δ-blockers) and that these are κ-sites.
Mechanisms underlying the cardiovascular responses to intrathecal vasopressin administration in rats
Authors: Riphagen Colleen L. , Pittman Quentin J.
Published: April 2011

Vasopressinergic pathways within the spinal cord have been implicated in the control of cardiovascular function. This study was undertaken to determine the mechanisms whereby intrathecally administered arginine vasopressin (AVP) increases blood pressure and heart rate in anesthetized rats. The cardiovascular responses to intrathecal AVP administration were significantly attenuated after intravenous administration of the ganglionic blocking agent, chlorisondamine chloride, as were the pressor responses following α-adrenergic receptor blockade with phentolamine and the heart rate responses following β-receptor blockade with propranolol. Intrathecal administration of the V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP completely blocked the cardiovascular responses to intrathecal AVP injections, but did not significantly alter the responses to intrathecal substance P injections. There was no evidence for the involvement of the rennin–angiotensin system in the pressor responses to intrathecal AVP, as (i) an angiotensin II receptor blocking agent, [Sar1, Val5, Ala8]angiotensin, failed to significantly alter the responses to intrathecal AVP, and (ii) plasma renin levels did not change following administration of the peptide. Intrathecal injections of [3H]AVP suggest that only small amounts of the peptide may cross into the plasma during the time in which the cardiovascular variables are changing. These data provide evidence that intrathecally administered AVP discretely activates the sympathetic outflow to the heart and vasculature, and confirm the neurally mediated nature of the response.Key words: blood pressure, spinal cord, peptides, autonomic nervous system, neurotransmitter.
Some pharmacological activities of novel adenine-related compounds isolated from a marine sponge Agelas mauritiana
Authors: Fathi-Afshar R. , Allen T. M. , Krueger C. A. , Cook D. A. , Clanachan A. S. , Vriend R. , Baer H. P. , Cass C. E.
Published: April 2011

Agelasimine A and agelasimine B, two novel compounds related to adenine, have been isolated from the orange sponge, Agelas mauritiana, and have been tested for a variety of biological activities. Both compounds inhibited proliferation of cultured L1210 leukemia cells at nanomolar concentrations with accumulation in the G1 stage of the cell cycle. However, no prolongation of life was observed in mice bearing P388 leukemia treated with these compounds. In the rat isolated aorta, micromolar concentrations of agelasimines were very effective in inhibiting contractions elicited by potassium chloride but had little or no effect on responses for prostaglandin F2α and had modest effects on the responses to noradrenaline and significant effects on 5-hydroxytryptamine. Agelsamines A and B appeared to be equipotent in causing relaxation in rabbit jejunum and bovine coronary artery, and they also inhibited nucleoside transport into rabbit erythrocytes in micromolar concentrations.Key words: natural products, adenine, cytotoxic compounds, smooth muscle, Ca2+ channel antagonist.
Analysis of the direct and indirect effects of adenosine on atrial and ventricular cardiac muscle
Authors: Wilson Andrew N. A. , Broadley Kenneth J.
Published: April 2011

The effects of adenosine were examined upon the tension developed by isolated paced left atria, left ventricular papillary muscles, and right ventricular strips, and upon the spontaneous rate of contraction of right atria of guinea pigs. Three aspects of the direct and indirect actions were examined: the direct effects upon resting developed tension and rate, the indirect activity when added to tissues prestimulated by isoprenaline, and the indirect activity upon isoprenaline concentration–response curves when added prior to exposure to isoprenaline. The direct effects on the atria were decreases in left atrial tension and right atrial rate. These responses were antagonized by 8-phenyltheophylline (8-PT) and therefore were due to stimulation of cell surface P1 purinoceptors. This antagonism was greater in the left atria than the right. The direct ventricular effects were, in contrast, increases in force of contraction, which were not antagonized by 8-PT. This positive inotropy was also unaffected by reserpine pretreatment of the guinea pigs and therefore not due to release of endogenous catecholamines. A possible intracellular effect of adenosine is discussed. Adenosine reduced the isoprenaline-prestimulated tension or rate in both atrial and ventricular tissues, and this indirect effect was susceptible to antagonism by 8-PT. In the presence of adenosine, concentration–response curves of the left and right atria for isoprenaline were displaced to the right, and the maxima were reduced. In contrast, there was no antagonism of the papillary muscle curves to isoprenaline, but the maximum developed tension was elevated. The minimal inhibitory effects of adenosine in ventricular muscles and the high concentrations required are discussed in the context of a physiological role for endogenous adenosine in attenuating cardiac overstimulation by the sympathetic nervous system or endogenously released catecholamines.Key words: adenosine, atria, ventricle, guinea pig, indirect and direct actions, 8-phenyltheophylline.
Influence of platelet-activating factor on leukotriene D4-induced contractions of the guinea pig parenchymal strip
Authors: Yaghi A. , Hamilton J. T. , Paterson N. A. M.
Published: April 2011

Platelet-activating factor (PAF) and sulphidopeptide leukotrienes, such as leukotriene D4 (LTD4), are potent constrictors that are probably released simultaneously in a variety of inflammatory respiratory events. The purpose of the present study was to determine whether LTD4-induced contractions of guinea pig parenchymal lung strips (GPPS) are modified in the presence of PAF. The contractile responses of isolated GPPS to cumulative doses of LTD4, acetylcholine, histamine, and potassium chloride in the presence of PAF (0.1 nM, 0.1 μM) were compared with parallel controls. There was no significant alteration of the response to acetylcholine and potassium chloride and the PAF-induced inhibition of the response to histamine, although significant, was not concentration dependent. In contrast, PAF in a concentration range from 0.1 nM to 1.0 μM caused a marked, concentration-dependent reduction of LTD4-induced contractions. Pretreatment with the PAF receptor antagonist, BN52021, prevented the attenuation of LTD4-induced contraction by PAF. The attenuation of LTD4-induced contraction by PAF was also prevented by pretreatment with indomethacin or with the thromboxane synthase inhibitor U63,557A, but not by pretreatment with the lipoxygenase inhibitors BW755c or nordihydroguaiaretic acid. Thus inhibition of LTD4-induced GPPS contraction by PAF is receptor dependent and probably secondary to thromboxane generation. The respiratory smooth muscle response to leukotrienes may be modified significantly by concomitant PAF release.Key words: platelet-activating factor, leukotriene D4, lung, parenchymal strip, guinea pig.
Plasma vasopressin and atrial natriuretic factor in response to blood volume changes in the anaesthetized rabbit
Authors: Courneya C. A. , Wilson N. , Ledsome J. R.
Published: April 2011

The influence of aortic baroreceptors and vagal afferent nerves on the release of immunoreactive vasopressin (iVP) and immunoreactive atrial natriuretic factor (iANF) was examined in anaesthetized rabbits. Changes in plasma concentrations of iVP and iANF, heart rate, mean arterial pressure, and right atrial pressure were measured in response to blood volume changes (+20, +10, −10, −20%). Carotid sinus pressure was maintained at 100 mmHg (1 mmHg = 133.3 Pa), and blood volume changes were performed before and after bilateral vagotomy (VNX) in all experiments. Two experimental groups were studied: rabbits with aortic depressor nerves intact (ADNI) and those with aortic depressor nerves sectioned (ADNX). Mean arterial and right atrial pressures decreased during haemorrhage and increased in response to volume expansion. Plasma iVP concentrations increased with haemorrhage and decreased with volume expansion in the ADNI group. Plasma iANF, however, decreased with haemorrhage and increased during volume expansion in both ADNI and ADNX groups. Vagotomy caused an increase in baseline plasma iANF in the ADNX group. The responses of iANF to blood volume changes were augmented after VNX and ADNX. The results show that neither the aortic baroreceptor nor the vagal afferent input are needed for the iANF response to changes in blood volume, over the range of ± 20%. In contrast, intact aortic baroreceptors are essential for changes in circulating iVP in this preparation.Key words: vasopressin, atrial natriuretic factor, blood volume, aortic baroreceptors, vagal afferents.
The role of exercise in thermogenesis and energy balance
Authors: Richard Denis , Rivest Serge
Published: April 2011

The role of exercise training in energy balance has been reviewed. Recent well-conducted studies showed that exercise may increase energy expenditure not only during the period of exercise itself but during the postexercise period as well. This notion of excess postexercise oxygen consumption (EPOC), which has been a controversial issue for many years, is now becoming a generally well-accepted concept, the consensus being that EPOC takes place following prolonged and strenuous exercise bouts. Besides, the role of EPOC in long-term energy balance remains to be determined. Long-term energy balance studies carried out in rats show that exercise affects energy balance by altering food intake and promoting energy expenditure. In male rats exercise causes a marked decrease in energy intake which contributes, in association with the expenditure of exercise itself, to retard lean and fat tissue growth. From the suppressed deposition of lean body mass, decreases in basal metabolic rate can be predicted in males. In female rats, exercise does not affect food intake; the lower energy gain of exercise-trained females results from the elevated expenditure rate associated with exercise itself. In both male and female rats, there is no evidence that exercise training affects energy expenditure other than during exercise itself unless the habitual feeding pattern of the rats is radically modified. The interactive effects of diet and exercise, which have to be further investigated in long-term energy balance, emerge as a promising area of research.Key words: exercise training, nutritional energetics, brown adipose tissue, diet-induced thermogenesis, body composition.
Superoxide radical production in plasma membrane samples from regressing rat corpora lutea
Authors: Sawada Masaaki , Carlson John C.
Published: April 2011

Plasma membrane samples prepared from regressing rat corpora lutea were examined for production of the superoxide radical. A procedure was developed to purify membrane samples that were enriched approximately 15-fold with the plasma membrane marker enzyme, and superoxide radical levels were determined using electron spin resonance to measure Tiron semiquinone. During prostaglandin F2α-induced and spontaneous regression, there was a significant increase in formation of superoxide radical that was not observed in plasma membrane samples from nonregressing corpora lutea. Plasma membrane incubation experiments indicated that the increase in production was temperature sensitive and reduced with inhibitors of phospholipase A2 and cyclooxygenase. Addition of superoxide dismutase or vitamin E abolished superoxide radical formation in vitro. Following the rise in superoxide radical levels during regression, there was also a significant decrease in the activity of the plasma membrane enzyme, Na+–K+ ATPase. These results indicate that the production of superoxide radical increases in plasma membrane samples prepared from regressing rat corpora lutea and that this increase is mainly due to the products of phospholipase A2 and cyclooxygenase activity.Key words: superoxide radical, plasma membrane, luteolysis.
Leukotriene D4 and platelet-activating factor – acether antagonists on allergic and arachidonic acid-induced reactions in guinea pig airways
Authors: Burka John F. , Briand Heather , Scott-Savage Peter , Pasutto Franco M.
Published: April 2011

Arachidonic acid (AA) and ovalbumin (OA) were used to induce contractions of sensitized guinea pig tracheal spiral (indomethacin-pretreated) and lung parenchymal strip preparations. This model was used to examine the properties of three leukotriene (LT) D4 antagonists and a platelet-activating factor (PAF)–acether receptor antagonist. The three LTD4 antagonists, L-649,923, FPL 57231, and LY163443, inhibited AA-induced contractions of indomethacin-pretreated tracheal spirals selectively. The PAF–acether antagonist, L-652,731, did not inhibit AA-induced contractions of either trachea or parenchyma. This confirmed that AA-induced contractions of trachea involved release and activity of LTD4. The LTD4 antagonists and L-652,731 partially inhibited OA-induced contractions of both trachea and parenchyma. When L-649,923 and L-652,731 or FPL 57231 and L-652,731 were combined, an additive inhibitory effect on OA-induced contractions was observed. When LY163443 and L-652,731 were combined, the inhibitory effect was synergistic. This may be due to the additional effect of LY163443 to inhibit phosphodiesterase. Total inhibition of OA-induced contractions was obtainable with relatively low concentrations when a LTD4 and PAF–acether antagonist were combined. These results suggested that LTD4 and PAF–acether may be the two major mediators in our model of allergic bronchospasm. The LTD4 and PAF–acether antagonists had the capacity to decrease baseline tone, even on tissues that were already relaxed with indomethacin, suggesting that LTD4 and PAF–acether may contribute to intrinsic tone in airway smooth muscle.Key words: leukotriene D4, platelet-activating factor, airway smooth muscle, antagonists, allergic bronchospasm.
The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats
Authors: Perks A. M. , Cassin S.
Published: April 2011

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6–39.2 mU/(kg∙min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg∙min)). The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30–6.72 μg/(kg∙min); 1–2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.Key words: fetal goats, lung liquid, arginine vasopressin, epinephrine.
Ca2+ channels in chick neural retina cells characterized by 1,4-dihydropyridine antagonists and activators
Authors: Wei X. Y. , Rutledge A. , Zhong Q. , Ferrante J. , Triggle D. J.
Published: April 2011

The voltage-sensitive calcium channel in cultured chick neural retina cells was characterized by the actions of the enantiomers of Bay K 8644 and 202-791 and other 1,4-dihydropyridines. These cells showed time- and voltage-dependent Ca2+ uptake that was stimulated by K+ depolarization and blocked by the inorganic calcium channel blockers Cd2+ and Co2+. A small fraction only (15% maximum) of the uptake was inactivated by predepolarization of the cells with 80 mM K+. Ca2+ uptake was sensitive to the 1,4-dihydropyridine calcium channel antagonists and activators. (S)-Bay K 8644 and (S)-202-791 stimulated the Ca2+ uptake, and (R)-Bay K 8644 and (R)-202-791 as well as nitrendipine and PN 200-110 inhibited Ca2+ uptake stimulated by K+ depolarization or channel activators. The K+ depolarization-stimulated uptake was inhibited by 90%, but the activator-stimulated uptake was completely blocked by the 1,4-dihydropyridine antagonists. The potencies of these agents as inhibitors of Ca2+ uptake were significantly lower than the binding affinities in membrane preparations from the same cells or their binding and pharmacologic affinities in vascular smooth muscle. K+ depolarization or (S)-Bay K 8644 induced 45Ca2+ uptake was not observed in a glial cell culture. [3H]Nitrendipine and [3H]PN 200-110 bound to membrane preparations of the cells consistent with the presence of a single type of high affinity binding site. [3H]PN 200-110 bound with higher affinity (KD = 7.09 ± 0.90 × 10−11 M) than did [3H]nitrendipine (KD = 4.10 ± 0.92 × 10−10 M), but the Bmax values were similar for the two ligands (98.9 ± 4.1 and 99.4 ± 6.58 fmol/mg protein, respectively). The discrepancy between binding and pharmacologic activities of the antagonist ligands does not appear to be due to the presence of 1,4-dihydropyridine-insensitive Ca2+ channels, but may relate to the inability of these agents to access a high affinity inactivated state in the intact cell or to the presence of discrete categories of binding sites. This marked discrepancy between affinities does not exist for the activator ligands studied. This study confirms the presence of voltage-dependent 1,4-dihydropyridine sensitive Ca2+ channels in chick neural retina cells.Key words: Ca2+ channels, 1,4-dihydropyridines, chick neural retina, retinal neurons.
Chronotropic function in spontaneously diabetic BB rats
Authors: Ramanadham Sasanka , McGrath Gail M. , McNeill John H.
Published: April 2011

In the present study, isolated atrial function in spontaneously diabetic BB Wistar rats maintained for 12 weeks on a low (BB-LI) and a high (BB-HI) dosage of insulin was examined. Basal atrial rates were unchanged in the diabetic animals, relative to nondiabetic littermates (ND-BB) or Wistar controls. The BB-HI animals were euglycemic and responded to isoproterenol in a similar manner to the ND-BB and Wistar control animals. In contrast, BB-LI animals remained hyperglycemic and exhibited lower responses to the maximum chronotropic effects of isoproterenol. Plasma thyroid hormone levels were unaltered in the BB-diabetic animals. These results therefore reveal an absence of bradycardia and hypothyroidism in spontaneously diabetic BB rats, in contrast to previous observations in streptozotocin diabetic rats. However, a decrease in chronotropic response to isoproterenol was still noted in the BB-LI animals. These findings suggest that decreased positive chronotropic effect of isoproterenol in diabetes may not be a direct consequence of altered thyroid status.Key words: BB Wistar rat, diabetes, chronotropic response, β-receptors.
Antitussive agents as N-methylaspartate antagonists: further studies
Authors: Church John , Jones Martyn G. , Davies Stephen N. , Lodge David
Published: April 2011

The relative potencies of ketamine and the morphinan derivatives dextrorphan, dextromethorphan, and levorphanol as antagonists of the excitatory actions of N-methylaspartate on rat spinal neurones in vivo were examined, both following their microelectrophoretic administration and, with the exception of levorphanol, after intravenous injection. Applied microelectro-phoretically, dextrorphan was a more potent N-methylaspartate antagonist than ketamine, levorphanol, or dextromethorphan. After systemic administration, however, dextrorphan was rather less potent than ketamine in this respect, whereas dextromethorphan remained less potent than either ketamine or dextrorphan. Noscapine, an antitussive that lacks anticonvulsant activity, failed to reduce selectively responses to N-methylaspartate as did papaverine, an isoquinoline structurally related to noscapine, and triprolidine, an antihistamine commonly found in proprietary cough medicines. The results are discussed with particular reference to the potential of the compounds tested as anticonvulsant and neuroprotective agents in vivo.Key words: dextrorphan, dextromethorphan, antitussive, N-methylaspartate, excitatory amino acid.
A fetal-instrumented model to study age-specific responses to leukotriene D4 and prostaglandin D2 in unsedated newborn lambs
Authors: Coe J. Y. , Olley P. M. , Coceani F.
Published: April 2011

Sequential studies of the pulmonary vascular response to leukotriene D4 (LTD4) and prostaglandin D2 (PGD2) in the immediate newborn period were performed in lambs, instrumented in utero and delivered vaginally. Compounds were tested in fully conscious 1.5-day-old lambs and the study was repeated 1 week later. Bolus injections of PGD2 (0.05–2.0 μg/kg) or LTD4 (0.01–1.0 μg/kg) were made into the main pulmonary artery or aorta while pulmonary blood flow and aortic, pulmonary artery, and left and right atrial pressures were monitored continuously. PGD2 was a systemic constrictor regardless of age. In lambs 1.5 days of age, it decreased pulmonary vascular pressure and resistance by 6% (p < 0.05) and 15% (p < 0.05), respectively, while 1 week later it increased pulmonary vascular resistance by 18% (p < 0.05). In contrast, LTD4 was a pulmonary and systemic vasoconstrictor in both the early and late newborn, the threshold dose being between 0.01 and 0.05 μg/kg at either age. The decrease in pulmonary blood flow and the increase in pressure and resistance were greater in older animals. In lambs 1.5 days of age, LTD4 (1 μg/kg) increased pulmonary vascular resistance by 66.1% (p < 0.05) and 1 week later by 210% (p < 0.001). These sequential observations in the same animal indicate that unlike PGD2, LTD4 is a pulmonary vasoconstrictor regardless of age, and its effectiveness increases significantly with age. These results support previous reports that PGD2 action in the pulmonary circulation changes shortly after birth from dilation to constriction.Key words: pulmonary circulation, newborn lamb, prostaglandin D2, leukotriene D4.