bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraethylammonium-evoked oscillatory contractions of rat tail artery: A K-K model
Authors: Wu Lingyun , Wang Zunzhe , Wang Rui
Published: April 2011

Spontaneously rhythmic contraction of peripheral blood vessels actively modulates the peripheral circulation and blood pressure. However, the underlying mechanisms for the complex rhythmic contraction patterns of various vascular tissues are not yet fully understood. In the present study, the tetraethylammonium (TEA)-induced spontaneously oscillatory contractions of isolated rat tail artery tissues were examined. It was found that TEA evoked arterial oscillatory contractions in a concentration-dependent, but endothelium-independent manner. The voltage- dependent K+(Kv) channel specific blocker, 4-aminopyridine (4-AP), induced a sustained, but not oscillated, vascular contraction. The presence of 4-AP had no effect on the TEA-induced oscillatory contractions. The blockade of KCachannels with charybdotoxin or apamin did not affect the basal force of vascular tissues. Neither the TEA-induced oscillatory contraction was affected by these blockers. The opening of KATPchannels by levcromakalim or their blockade by glybenclamide ceased or increased, respectively, the oscillation of TEA-induced contractions. The absence of Ca2+or the presence of nifedipine in the bath solution completely abolished the effects of TEA. The inhibition of Ca2+-ATPase in the sarcoplasmic reticulum with micromolar concentrations of thapsigargin or cyclopiazonic acid either abolished or enhanced, respectively, the TEA-induced oscillatory contractions. Ryanodine did not affect the TEA-induced oscillatory contraction. In conclusion, the TEA-induced oscillatory contraction may be initiated by the blockade of the TEA-sensitive delayed rectifier K+channels and maintained by the TEA-insensitive but ATP-sensitive K+channels. This K-K model presents a novel mechanism for the depolarization-induced rhythmic contractions of small arteries.Key words: KATPchannels, Kv channels, rhythmic contraction, tetraethylammonium, vascular smooth muscle.
Effect of stevioside on PAH transport by isolated perfused rabbit renal proximal tubule
Authors: Jutabha Promsuk , Toskulkao Chaivat , Chatsudthipong Varanuj
Published: April 2011

Stevioside, a non-caloric sweetening agent, is used as a sugar substitute. An influence of stevioside on renal function has been suggested, but little is known about its effect on tubular function. Therefore, the present study was designed to explore the direct effect of stevioside on transepithelial transport of p-aminohippurate (PAH) in isolated S2segments of rabbit proximal renal tubules using in vitro microperfusion. Addition of stevioside at a concentration of 0.45 mM to either the tubular lumen, bathing medium, or both at the same time had no effect on transepithelial transport of PAH. Similarly, a concentration of 0.70 mM (maximum solubility in the buffer) when present in the lumen, had no effect on PAH transport. However, this concentration in the bathing medium inhibited PAH transport significantly by about 25-35%. The inhibitory effect of stevioside was gradually abolished after it was removed from the bath. Addition of 0.70 mM stevioside to both lumen and bathing medium at the same time produced no added inhibitory effect. Stevioside at this concentration has no effect on Na+/K+-ATPase activity as well as cell ATP content. These findings suggest that stevioside, at a pharmacological concentration of 0.70 mM, inhibits transepithelial transport of PAH by interfering with the basolateral entry step, the rate-limiting step for transepithelial transport. The lack of effect of stevioside on transepithelial transport of PAH on the luminal side and its reversible inhibitory effect on the basolateral side indicate that stevioside does not permanently change PAH transport and should not harm renal tubular function at normal human intake levels.Key words: stevioside, p-aminohippurate, renal proximal tubule.
Dietary zinc deficiency and expression of T lymphocyte signal transduction proteins
Authors: Taylor Carla G , Giesbrecht Jeri-Anne C
Published: April 2011

Impaired immune function in dietary zinc (Zn) deficiency is characterized in part by reduced lymphocyte numbers (lymphopenia) and depressed cell-mediated (T lymphocyte) immune function, however, the causative mechanisms at the molecular level have not been elucidated. This paper will focus on the role of dietary Zn in T lymphocyte signal transduction, and specifically, the early Zn-dependent steps for phosphorylation and the putative Zn-finger proteins or Zn-metalloenzymes that may be part of the molecular mechanism for explaining immune dysfunction in Zn deficiency. One of the major recent findings is that murine splenic T lymphocyte p56lckexpression is elevated in dietary Zn deficiency and caloric deficiency. Based on the known functions of p56lck, it is proposed that elevated p56lckmay contribute to altered thymocyte maturation, apoptosis, and lymphopenia in dietary Zn deficiency and other malnutrition syndromes.Key words: zinc, T lymphocytes, signal transduction, immune function.
Mechanisms of vanadium action: insulin-mimetic or insulin-enhancing agent?
Authors: Cam Margaret C , Brownsey Roger W , McNeill John H
Published: April 2011

The demonstration that the trace element vanadium has insulin-like properties in isolated cells and tissues and in vivo has generated considerable enthusiasm for its potential therapeutic value in human diabetes. However, the mechanisms by which vanadium induces its metabolic effects in vivo remain poorly understood, and whether vanadium directly mimics or rather enhances insulin effects is considered in this review. It is clear that vanadium treatment results in the correction of several diabetes-related abnormalities in carbohydrate and lipid metabolism, and in gene expression. However, many of these in vivo insulin-like effects can be ascribed to the reversal of defects that are secondary to hyperglycemia. The observations that the glucose-lowering effect of vanadium depends on the presence of endogenous insulin whereas metabolic homeostasis in control animals appears not to be affected, suggest that vanadium does not act completely independently in vivo, but augments tissue sensitivity to low levels of plasma insulin. Another crucial consideration is one of dose-dependency in that insulin-like effects of vanadium in isolated cells are often demonstrated at high concentrations that are not normally achieved by chronic treatment in vivo and may induce toxic side effects. In addition, vanadium appears to be selective for specific actions of insulin in some tissues while failing to influence others. As the intracellular active forms of vanadium are not precisely defined, the site(s) of action of vanadium in metabolic and signal transduction pathways is still unknown. In this review, we therefore examine the evidence for and against the concept that vanadium is truly an insulin-mimetic agent at low concentrations in vivo. In considering the effects of vanadium on carbohydrate and lipid metabolism, we conclude that vanadium acts not globally, but selectively and by enhancing, rather than by mimicking the effects of insulin in vivo.Key words: vanadium, insulin-mimetic, insulin-like, insulin-enhancing.
Inhibition of small conductance K+-channels attenuated melatonin-induced relaxation of serotonin-contracted rat gastric fundus
Authors: Storr M , Schusdziarra V , Allescher H -D
Published: April 2011

The aim of this study was to investigate the effects of melatonin on rat gastric fundus smooth muscle. Melatonin (10-4 to10-3 M) had no effect on the basal tone of gastric smooth muscle. After precontraction with carbachol (10-6 M) or serotonin (10-7 M), melatonin caused a concentration dependent inhibitory action. The half maximal effect on serotonin-induced contraction was found with 1.12 beta 0.86 beta 10-5 M of melatonin. Increasing concentrations of melatonin (10-5 to 10-3 M) resulted in a right shift of the serotonin concentration response curve (10-10 to10-5 M). This inhibitory effect of melatonin was partially blocked in the presence of apamin (10-10 to 10-7 M), a specific blocker of the small conductance calcium-dependent potassium channel, but not in the presence of other potassium channel blockers like charybdotoxin (10-8 M), glibenclamide (10-5 M), or tetraethylammonium (ODQ, 10-4 M). The inhibitory effect was not changed in the presence of the neuronal blocker tetrodotoxin (10-6 M), the selective P2-receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 × 10-5 M), the nitric-oxide synthase inhibitor N-nitro-L-arginine (3 × 10-4 M), or the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (10-4 M), suggesting that neither the purinergic, nitrergic, nor guanylate cyclase pathways were involved. We further investigated inhibitory responses to electrical field stimulation (EFS) at different frequencies under non-adrenergic, non-cholinergic (NANC) conditions on a serotonin-induced contraction in the presence of melatonin (10-5 to 10-4 M). Melatonin significantly reduced these inhibitory NANC responses in higher (8-32 Hz), but not lower (05-4 Hz), frequencies (16 Hz without melatonin, 103 ± 6.3%; melatonin 10-5 M, 80.4 ± 7.5%; melatonin 10-4 M, 39.1 ± 17.1%). Melatonin had no effect on contractile responses induced by EFS under basal tone. These results demonstrate that the inhibitory effect of melatonin in rat gastric fundus smooth muscle is apamin sensitive, but is not affected by other potassium channel blockers. This suggests that melatonin may be another transmitter candidate for the apamin sensitive responses within the gastrointestinal tract.Key words: melatonin, smooth muscle, apamin, NANC-inhibition, gastric, potassium channels.
Instigation and control of treadmill locomotion in high decerebrate cats by stimulation of the hook bundle of Russell in the cerebellum
Authors: Mori Shigemi , Matsui Toshihiro , Mori Futoshi , Nakajima Katsumi , Matsuyama Kiyoji
Published: April 2011

In high decerebrate cats, pulse train microstimulation of a restricted region of the midline cerebellar white matter produced a generalized increase in postural muscle tone in the neck, trunk, and limb extensor muscles, and air-stepping of all four legs on a stationary surface. On the moving belt of a treadmill, such stimulation produced well coordinated, fore- and hindlimb locomotion as evoked by stimulating the mesencephalic locomotor region (MLR). Microinjection of a neural tracer into the cerebellar locomotion-inducing site resulted in a bilateral retrograde labeling of cells limited to the fastigial nuclei simultaneously with anterograde labeling of fibers projecting bilaterally to the medial pontomedullary reticular formation (mPMRF) the vestibular complex and upper cervical segments. These results have led to our proposition that the effective cerebellar locomotor region (CLR) corresponds to the midline region of the hook bundle of Russell. Passing through this structure are crossed fastigioreticular and fastigiovestibular fibers, together with fastigiospinal fibers. Subsequently, we showed that CLR stimulation resulted in simultaneous short-latency synaptic activation of long-descending reticulospinal and vestibulospinal cells with high synaptic security. Clearly, the fastigial nucleus possesses potential capability to recruit and regulate posture- and locomotor-related subprograms which are distributed within the brainstem and spinal cord by the in-parallel activation of fastigiospinal, fastigioreticular, and fastigiovestibular pathways.Key words: cerebellar locomotor region (CLR), fastigial nucleus, hook bundle of Russell, reticulospinal cell, vestibulospinal cell.
Differential alteration of cytochrome P450 isoenzymes in two experimental models of cirrhosis
Authors: Bastien Marie-Claude , Leblond François , Pichette Vincent , Villeneuve Jean-Pierre
Published: April 2011

Liver diseases are associated with a decrease in hepatic drug elimination, but there is evidence that cirrhosis does not result in uniform changes of cytochrome P450 (CYP) isoenzymes. The objective of this study was to determine the content and activity of four CYP isoenzymes in the bile duct ligation and carbon tetrachloride (CCl4)-induced models of cirrhosis. The hepatic content of CYP1A, CYP2C, CYP2E1, and CYP3A was measured by Western blot analysis. CYP activity in vivo was evaluated with breath tests using substrates specific for different isoenzymes: caffeine (CYP1A2), aminopyrine (CYP2C11), nitrosodimethylamine (CYP2E1), and erythromycin (CYP3A). Bile duct ligation resulted in biliary cirrhosis; CYP1A, CYP2C and CYP3A content was decreased and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas CYP2E1 content and the nitrosodimethylamine breath test were unchanged compared with controls. CCl4treatment resulted in cirrhosis of varying severity as assessed from the decrease in liver weight and serum albumin. In rats with mild cirrhosis, CYP content was comparable with controls except for a decrease in CYP2C. The activity of CYPs was also unchanged except for an increase in CYP2E1 activity. In rats with more severe cirrhosis, the content of all four CYP isoenzymes and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas the nitrosodimethylamine breath test was unchanged. In both models of cirrhosis, there was a significant correlation between the breath tests results and the severity of cirrhosis as assessed from serum albumin levels. These results indicate that content and the catalytic activity of individual CYP enzymes are differentially altered by cirrhosis in the rat and also suggest that drug probes could be useful to assess hepatic functional reserve.Key words: breath test, cirrhosis, cytochrome P450, bile duct ligation, carbon tetrachloride.
Calcium and growth responses of hyperresponsive airway smooth muscle to different isoforms of platelet-derived growth factor (PDGF)
Authors: Zacour Mary E , Tolloczko Barbara , Martin James G
Published: April 2011

Airway smooth muscle (ASM) mass is likely to be an important determinant of airway responsiveness. Highly inbred Fisher rats model innate hyperresponsiveness, and also have more ASM in vivo than control Lewis rats. Platelet derived growth factor (PDGF) is an important endogenous growth factor for ASM, and partially purified PDGF-AB causes enhanced growth of Fisher rat ASM cells, compared to Lewis cells. The aim of the present study was to determine the mitogenic effects of all three recombinant PDGF isoforms on ASM cells, and investigate the mechanisms of enhanced Fisher ASM growth responses. The potential mechanisms assessed include PDGF receptor expression and activation (tyrosine phoshorylation), and intracellular calcium (Ca2+) responses to PDGF isoforms. Fisher ASM cells had a greater mitogenic response to PDGF-AB and -AA, and a greater Ca2+response to -BB than Lewis ASM cells. A Ca2+response was not necessary for a mitogenic response, and the effects of PDGF isoforms on Ca2+were not associated with their effects on growth. Therefore, we suggest that enhanced Fisher mitogenic response to PDGF-AA and -AB is not mediated by differences in Ca2+signalling. Western analysis of the PDGF receptor indicated a similar expression of β-PDGF receptor in ASM cells from the two rat strains, but a greater expression of α-PDGF receptor in Fisher cells; however, phosphorylation of the PDGF receptor following growth stimulation did not differ between strains. This suggests a role for post-receptor signals, in addition to enhanced receptor expression, in the enhanced growth response of Fisher ASM cells to PDGF-AA and -AB.Key words: PDGF receptors, tyrosine phosphorylation, intracellular calcium, proliferation, airway smooth muscle cells.
Perturbations in factors that modulate osteoblast functions in vitamin B6 deficiency
Authors: Massé P G , Delvin E E , Hauschka P V , Donovan S M , Grynpas M D , Mahuren J D , Watkins B A , Howell D S
Published: April 2011

It was hypothesized that the widespread structural defect of collagen in connective tissue of vitamin B6deficient-animals and the consequent alteration in bone biomechanical properties cause an additional stress to their inflammed swollen tibiotarsometatarsal joints. The present study showed a 32% elevation (P < 0.02) in mean plasma free cortisol concentration. Vitamin D metabolism was impaired but without changing plasma calcium homeostasis and bone mineral content. Mean plasma calcitriol [1,25(OH)2D] concentration was significantly reduced (P < 0.001). Because plasma calcidiol concentration did not change, we speculated that either renal 25-hydroxycalciferol-1α-hydroxylase activity was reduced or 1,25(OH)2D turnover was increased. Plasma osteocalcin, an index of osteoblast function related to bone formation, was significantly decreased (P < 0.05). This adverse effect on osteoblasts was consistent with the reduction of bone specific alkaline phosphatase activity (another index of bone formation) found in a previous study. The excess of cortisol may have impaired these bone cells functions directly and (or) indirectly via the decline in calcitriol synthesis. Plasma hydroxyproline concentrations in B6-deficient animals were found to be significantly reduced (P < 0.001), suggesting that cortisol in excess had also a suppressive effect on another hydroxylase, namely tissue (mainly bone and liver) prolyl hydroxylase. The bone uncoupling (in formation and resoption) associated with vitamin B6deficiency seems to be due to secondary hypercortisolism and (or) another unknown factors but not related to a change in bone modulators such as IGF-1 and eicosanoids.Key words: collagen, vitamin B6, vitamin D, cortisol, osteocalcin, IGF-1, eicosanoids, PGE2.
Couplage électronique et transferts de charges dans l'ADN : étude du contrôle énergétique
Authors: Benrahmoune Mustapha , Filali-Mouhim Abdelali , Jay-Gerin Jean-Paul
Published: April 2011

The influence of the energetic gap on the effective distance-decay rate of electronic coupling (βeff) in DNA is investigated in the context of the superexchange mechanism. The DNA double helix is described by a tight-binding electronic Hamiltonian model, in which all orbitals have the same energy and interact with one another through an exponentially decaying function of distance. Our numerical results concerning the βeff values obtained for two different DNA molecules are analyzed within the theoretical framework of the "continuous-medium approximation," previously developed by Lopez-Castillo et al. (J.-M. Lopez-Castillo, A. Filali-Mouhim, I.L. Plante, and J.-P. Jay-Gerin. J. Phys. Chem. 99 : 6864-6875, 1995). We find that the intervening DNA bridge between the donor and acceptor sites is defined by a unique dimensionless control parameter Γ/E, where E is the energy of the orbitals of this medium with respect to those of the redox site orbitals (energetic gap) and Γ is the electronic band width of the bridge considered as a continuous medium. In the narrow-band regime, our "through-space" coupling model predicts βeff values that are in good order of magnitude agreement with those calculated by other theoretical approaches as well as with those obtained from experiment. Moreover, under equivalent energetic conditions, the DNA-mediated transfers of holes and electrons differ considerably. This difference depends upon the sign of the parameter Γ/E.Key words: DNA, electronic coupling, effective distance-decay rate, energetic gap, superexchange mechanism, continuous-medium approximation, long-distance electron and hole transfers.
A comparison of the kinetics of low-density lipoprotein oxidation induced by copper or by γ-rays: Influence of radiation dose-rate and copper concentration
Authors: Khalil Abdelouahed , Fülöp Tamàs
Published: April 2011

The oxidation of low-density lipoproteins is the first step in the complex process leading to atherosclerosis. The aim of our study was to compare the kinetics of low density lipoprotein oxidation induced by copper ions or by oxygen free radicals generated by60Co γ-rays. The effects of copper concentration and irradiation dose-rate on LDL peroxidation kinetics were also studied. The oxidation of LDL was followed by the measurement of conjugated diene, hydroperoxides, and thiobarbituric acid reactive substance formation as well as α-tocopherol disappearance. In the case of gamma irradiation, the lag-phase before the onset of lipid peroxidation was inversely correlated to the radiation dose-rate. The radiation chemical rates (v) increased with increasing dose-rate. Copper-induced LDL peroxidation followed two kinetic patterns: a slow kinetic for copper concentrations between 520 µM, and a fast kinetic for a copper concentration of 40 µM. The concentration-dependent oxidation kinetics suggest the existence of a saturable copper binding site on apo-B. When compared with γ-rays, copper ions act as drastic and powerful oxidants only at higher concentrations ([Formula: see text]40 µM).Key words: LDL, peroxidation, kinetics, copper, γ-radiolysis, dose-rate.
Oxydation radiolytique du tamoxifène par les radicaux libres ·OH et (ou) HO·2
Authors: Leguéné C , Clavère P , Jore D , Gardès-Albert M
Published: April 2011

Tamoxifen is the most widely used antiestrogen in the treatment of breast cancer. In this work, we have studied its antioxidant properties. We have investigated the ability of tamoxifen to scavenge, in vitro, ·OH and (or) HO·2 free radicals that are produced by water radiolysis. Aqueous solutions of tamoxifen of concentrations ranging between 10-5 and 2.5 × 10-5 M have been irradiated (γ 137Cs) in aerated acidic medium (H3PO4 10-3 M or HCOOH 10-1 M). The results show that tamoxifen reacts quantitatively with ·OH free radicals but does not react with HO·2 free radicals under our experimental conditions.Key words: tamoxifen, antioxidant, oxygenated free radicals, radiolysis.
Role of 5-HT in the regulation of the brain-pituitary-adrenal axis: effects of 5-HT on adrenocortical cells
Authors: Contesse Vincent , Lefebvre Hervé , Lenglet Sébastien , Kuhn Jean-Marc , Delarue Catherine , Vaudry Hubert
Published: April 2011

Serotonin (5-HT) plays a pivotal role in the regulation of the brain-pituitary-adrenal axis. In particular, 5-HT has been shown to control the activity of hypothalamic CRF neurons and pituitary corticotrope cells through activation of 5-HT1Aand (or) 5-HT2A/2Creceptor subtypes. 5-HT, acting through 5-HT2receptors, can also trigger the renin-angiotensin system by stimulating renin secretion and consequently can enhance aldosterone production. At the adrenal level, 5-HT produced locally stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species. In the frog, rat, and pig adrenal gland, 5-HT is synthesized by chromaffin cells, while in the mouse adrenal cortex, 5-HT is contained in nerve fibers. In man, 5-HT is present in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates corticosteroid secretion in various species (including human). The type of receptor involved in the mechanism of action of 5-HT differs between the various species. In frogs and humans, the stimulatory effect of 5-HT on adrenocortical cells is mediated through a 5-HT4receptor subtype positively coupled to adenylyl cyclase and calcium influx. In the rat, the effect of 5-HT on aldosterone secretion is mediated via activation of 5-HT7receptors. Clinical studies indicate that 5-HT4receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with corticotropic insufficiency and primary hyperaldosteronism. Local serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex as well as in the pathophysiology of cortisol and aldosterone disorders.Key words: HPA axis, renin-angiotensin system, adrenal gland, corticosteroid secretion, serotonergic receptors.
Newt prolactin and its involvement in reproduction
Authors: Kikuyama S , Yazawa T , Abe S , Yamamoto K , Iwata T , Hoshi K , Hasunuma I , Mosconi G , Polzonetti-Magni A M
Published: April 2011

The amino acid sequence of newt (Cynops pyrrhogaster) prolactin deduced from the nucleotide sequence of its cDNA showed a relatively high homology with sequences of chicken and sea turtle prolactins as well as with those of anuran prolactins. Cynops prolactin receptor transcripts were detected in various tissues and organs, suggesting that prolactin plays multiple roles in urodeles. Urodele prolactin was purified from the pituitaries of C. pyrrhogaster. Antiserum against this prolactin was used for radioimmunoassay of plasma prolactin and immunoneutralization experiments. Endogenous prolactin was shown to induce migration to water, courtship behavior, and cessation of spermatocytogenesis in the Cynops newt. The hormone was found to be involved in the development of cloacal glands such as the lateral and abdominal glands, growth of the tail and Mauthner neurons, secretion of oviducal jelly, and enhanced synthesis of a female attracting pheromone (sodefrin), and responsiveness of the olfactory epithelium to sodefrin. In most of these cases, prolactin was found to act synergistically or antagonistically with sex steroids. We also discovered that hypersecretion of prolactin in the newts subjected to cold temperature was induced by hypothalamic stimulation rather than release from hypothalamic inhibition.Key words: prolactin, newts, reproduction.
Somatostatin family of peptides and its receptors in fish
Authors: Lin Xinwei , Otto Carla J , Cardenas Rodolfo , Peter Richard E
Published: April 2011

Somatostatin (SRIF or SS) is a phylogenetically ancient, multigene family of peptides. SRIF-14 is conserved with identical primary structure in species of all classes of vertebrates. The presence of multiple SRIF genes has been demonstrated in a number of fish species and could extend to tetrapods. Three distinct SRIF genes have been identified in goldfish. One of these genes, which encodes [Pro2]SRIF-14, is also present in sturgeon and African lungfish, and is closely associated with amphibian [Pro2,Met13]SRIF-14 gene and mammalian cortistatin gene. The post-translational processing of SRIF precursors could result in multiple forms of mature SRIF peptides, with differential abundance and tissue- or cell type-specific patterns. The main neuroendocrine role of SRIF-14 peptide that has been determined in fish is the inhibition of pituitary growth hormone secretion. The functions of SRIF-14 variant or larger forms of SRIF peptide and the regulation of SRIF gene expression remain to be explored. Type 1 and type 2 SRIF receptors have been identified from goldfish and a type 3 SRIF receptor has been identified from an electric fish. Fish SRIF receptors display considerable homology with mammalian counterparts in terms of primary structure and negative coupling to adenylate cyclase. Although additional types of receptors remain to be determined, identification of the multiple gene family of SRIF peptides and multiple types of SRIF receptors opens a new avenue for the study of physiological roles of SRIF, and the molecular and cellular mechanisms of SRIF action in fish.Key words: somatostatin, somatostatin receptor, growth hormone, fish.
Roles of the activin regulatory system in fish reproduction
Authors: Ge Wei
Published: April 2011

Activin (βAβA, βAβB, and βBβb) is a dimeric growth factor with diverse biological activities in vertebrate reproduction. Activin exerts its actions by binding to its specific type II and type I receptors. The activity of activin is regulated by follistatin, its binding protein, and the antagonists inhibin and antivin. All major components of the activin-inhibin-follistatin system have been identified in fish except the α subunit of inhibin. Using goldfish as a model, we have demonstrated that activin is expressed in the pituitary and the recombinant goldfish activin B has novel inverse effects on the expression of GTH β subunits. Activin increases the mRNA level of GTH-Iβ while significantly suppressing the expression of GTH-IIβ. We have also demonstrated the expression of activin and its receptors in the goldfish and zebrafish ovary. Using an in vitro ovarian follicle incubation as the system, we have investigated the involvement of the activin system in the process of final oocyte maturation. Our evidence clearly indicates that activin has potent effect of promoting final oocyte maturation, and that it may play a role in mediating the stimulatory effect of pituitary gonadotropin in the event of oocyte maturation. Key words: activin, inhibin, follistatin, fish, reproduction.
Perturbation of rat renal tubule transport of the organic cation amantadine in recent onset streptozotocin-induced diabetes and in uninephrectomy
Authors: Goralski Kerry B , Stupack Dwayne G , Hatch Grant M , Sitar Daniel S
Published: April 2011

The effects of early-stage diabetes mellitus and uninephrectomy on the renal tubule transport of amantadine were investigated. Kidney tubules were isolated from streptozotocin-induced diabetic (± insulin treatment), uninephrectomized, and control male Sprague-Dawley rats. There were no differences in the Km of amantadine uptake in renal proximal and distal tubules for the imposed treatments compared with control values. Vmax for amantadine uptake in the proximal tubules of diabetic and uninephrectomized rats was higher than the respective control (P < 0.05). Vmax for insulin-treated diabetic rats was similar to control values but was lower than that for untreated diabetic rats (P < 0.05). Vmax for distal tubule uptake was not altered by any treatment. Structure-activity studies demonstrated that bicarbonate-dependent amantadine uptake was inhibited by glycolate and lactate, but not by propionate or α-, β-, or γ-hydroxybutyrate. Early stage streptozotocin-induced diabetes mellitus and uninephrectomy induced changes in the kidney that resulted in a similar selective increase in proximal tubule amantadine uptake. These data represent the first description that experimentally induced diabetes mellitus and uninephrectomy modulate the function of the renal tubule organic cation (amantadine) transport system. Both interventions represent potential models in which phenotypic modulation of the renal elimination of organic cationic drugs may be achieved and studied.Key words: amantadine, organic cation transport, renal tubules, diabetes, uninephrectomy.
Damage induced arrhythmias: mechanisms and implications
Authors: ter Keurs Henk EDJ , Zhang Ying Ming , Davidoff Allen W , Boyden Penelope A , Wakayama Yu-ji , Miura Masahito
Published: April 2011

Little is known about the role played by non-uniform myocardial stress and strain distributions and by non-uniform excitation contraction coupling in mechanisms underlying the premature beats that initiate an arrhythmia. We will review the evidence in support of a mechanism in which both non-uniform contraction and increased Ca2+ load of cells adjacent to acutely damaged cells are essential in the "spontaneous" generation of Ca2+ transients during the relaxation phase of the electrically driven twitch. The putative mechanism of initiation of the propagating Ca2+ waves involves feedback of rapid length (or force) changes to dissociation of Ca2+ from the contractile filaments. A novel aspect of this concept is that these mechanically elicited Ca2+ transients induce propagating Ca2+ waves that travel into the adjacent normal myocardium and cause after-depolarizations, which, in turn, may cause premature action potentials. These premature action potentials will further load the cells with Ca2+, which promotes the subsequent generation of propagating Ca2+ transients and leads to triggered arrhythmias. The damage-induced premature beats may also initiate re-entry arrhythmias in non-uniform myocardium. These observations strongly support the concept that abnormal cellular Ca2+ transport plays a crucial role in the initiation of arrhythmias in damaged and non-uniform myocardium.Key words: cardiac muscle, excitation-contraction coupling, damage, Ca2+, and arrhythmias.
Reduced baroreceptor sensitivity during hypotension in ANP-knockout mice
Authors: Ackermann Uwe , Deliva Robin Donna
Published: April 2011

We studied baroreflex gain in inactin-anesthetized mice that had been genetically modified to be depleted of atrial natriuretic peptide (ANP -/-). Wild-type mice (ANP +/+) served as controls. ANP -/- mice had a significantly higher basal arterial blood pressure (ABP) than ANP +/+ mice [112 ± 7 vs. 80 ± 5 mmHg (mean ± SEM)]. Their basal heart rates were not different (491 ± 13 vs. 446 ± 19 bpm). A third group, composed of ANP +/+ mice only, was rendered acutely hypertensive by an intravenous infusion of arginine vasopressin acetate (0.3 pg bolus followed by 0.3 pg/h) so as to serve as a control for the elevated ABP in the ANP -/- mice. Transient changes in ABP were caused by bolus injections of oxymetazoline hydrochloride (1.5-3 ng) or sodium nitroprusside (20-100 ng). Baroreflex gain was calculated as the ratio of the peak heart rate change that followed the peak change in mean ABP resulting from injection of oxymetazoline or nitroprusside. There were no significant differences among the groups in their responses to transient hypertension. On the other hand, the ANP -/- mice showed a significantly depressed tachycardic response to transient hypotension when compared with the other two groups. We conclude that the ANP -/- mice are unable to increase efferent sympathetic nervous activity adequately above the high basal activity that is a feature of this animal model.Key words: atrial natriuretic peptides, knockouts, arterial blood pressure.
Epinephrine causes a reduction in lymph node cell output in sheep
Authors: Seabrook Timothy J , Ristevski Bill , Rhind Shawn G , Shek Pang N , Zamecnik Jiri , Shephard Roy J , Hay John B
Published: April 2011

The lymphatic system has a critical role in the return of fluids, proteins, and cells to the circulatory system. However, the effects of stress, including exercise, on this system have not been adequately studied. We investigated the effect of a physiological dose (1 mg) of epinephrine (Epi) on lymph flow, cell concentration, and lymphocyte subsets in efferent subcutaneous lymph in sheep. Blood leukocyte numbers, differential, lymphocyte subsets, and blood and lymph pools of lymphocytes were determined simultaneously. A significant acute increase in lymph flow was followed by a post-injection decrease in flow and cellular output. No changes in lymphocyte subsets or pools of lymphocytes were seen in either blood or lymph. The timing of elevated plasma and lymph concentrations of Epi and norepinephrine (NE) corresponded with the increased lymph flow. In conclusion, Epi injection caused no change in lymphocyte subset distribution, leukocyte concentration, or pools of lymphocytes. A decrease in lymph flow and cellularity was documented post-injection, indicating that lymphatic tissue has no role in the leukocytosis seen after Epi injection. Lymphocyte retention by lymph nodes, however, may contribute to post-injection lymphopenia.Key words: lymphocyte recirculation, catecholamines, exercise, stress, lymph.
Functional properties of the native type 3 ryanodine receptor Ca2+-release channel from canine diaphragm
Authors: Rousseau Eric , Proteau Sonia
Published: April 2011

mRNA and protein analyses have previously shown that the diaphragm expresses two ryanodine receptor isoforms: RyR1 and RyR3.RyR1 is the main Ca2+-releasing pathway in this muscle type. We now report the conducting, gating, and immunological properties of the native and purified forms of the less abundant RyR3 channel. The conductance of this native Ca2+-release channel was 330 pS in 50 mM/250 mM trans/cis CsCH3SO3. It was activated by Ca2+concentrations of 1-1000 µM, and did not inactivate at mM concentrations of Ca2+. Both isoforms were purified by either a sucrose density gradient or immunoprecipitation as > 450 kDa proteins on SDS-PAGE. Western blot analysis confirmed the presence of RyR1 and RyR3, which displayed conductances of 740 ± 30 and 800 ± 25 pS, respectively, in 250 mM KCl. We thus provide evidence that one form of the diaphragm SR Ca2+-release channels may be classified as RyR3, with gating properties different from those of the well-characterized RyR1 and RyR2 isoforms.Key words: diaphragm, calcium channel, ryanodine receptors, skeletal muscles, excitation-contraction coupling.
The Aplysia californica Cl- pump is a P-type ATPase: evidence through inhibition studies
Authors: Gerencser George A , Zhang Jianliang
Published: April 2011

Utilizing a proteoliposomal preparation containing Cl-ATPase from Aplysia californica foregut, it was shown that orthovanodate inhibited Cl-ATPase activity, ATP-dependent Cl transport, ATP-dependent membrane potential change and ATP-dependent phosphorylation. N-ethylmalemide and p-chloromercurobenzoate also inhibited the Cl pump biochemical and physiological transport characteristics. However, bafilomycin, azide, N, N'-dicyclohexylcarboiimide (DCCD), and efrapeptin had no effect on the Cl pump biochemical or physiological characteristics, suggesting that this Cl pump was a P-type ATPase. It was concluded that this P-type ATPase Cl pump is the mechanism that is responsible for the net absorptive flux of Cl in the A. californica foregut.Key words: Cl pump, P-type ATPase, orthovanadate.
Insulin-like peptides are not involved in maturation or functional recovery of neural circuits in the locust flight system
Authors: Gee Christine E , Robertson R Meldrum
Published: April 2011

We sought to manipulate maturation and functional recovery of locust flight circuitry by treating locusts with pharmacological doses of bovine anti-insulin and insulin. Anti-insulin treatment of maturing locusts caused reduced growth of the thoracic nervous system, lower body weight, and softer cuticles compared with control locusts. We were unable to block either maturation or recovery of flight circuitry with anti-insulin. We propose that insulin-related peptides are involved in growth and cuticular changes during adult maturation, but have no role in promoting neuronal sprouting during this period or as a result of injury.Key words: insulin, maturation, functional recovery, proprioceptors, flight.
Study of acute pharmacologic effects of prolactin on calcium and water transport in the rat colon by an in vivo perfusion technique
Authors: Krishnamra Nateetip , Ousingsawat Jiraporn , Limlomwongse Liangchai
Published: April 2011

We investigated the acute effect of intraperitoneally administered prolactin on calcium and water transport in colon of sexually mature female Wistar rats using an in vivo perfusion technique. Test solution containing (in mM) NaCl, 100; KCl, 4.7; MgSO4, 1.2; CaCl2, 20; D-glucose, 11; sodium ferrocyanide (Na4Fe(CN)6), an index of net water transport, 20; and 0.7 (µCi45CaCl2(1 Ci = 37 GBq) was perfused througth the 8-cm colonic loop for 60 min at perfusion rates of 0.5 or 1.0 mL·min1. Calcium and water transport was also studied under a no flow condition to stimulate the condition often found in the colon by in vivo ligated colonic loop for 30 min. Control results showed no correlation between calcium transport and water flux. Flow of luminal solution at 0.5 and 1.0 mL·min1was found to reverse net calcium absorption from 0.04 ± 0.01 nmol·g1dry weight·h1to net calcium secretion of 0.04 ± 0.04 and 0.9 ± 0.02 nmol·g1dry weight·h1, respectively. Neither 0.4, 0.6, nor 1.0 mg·kg1prolactin had any effect on calcium fluxes in the colon. On the other hand, at a perfusion rate of 1 mL·min1, 0.4 mg·kg1prolactin significantly decreased net water absorption from 3.86 ± 0.90 to 0.88 ± 0.64 mL·g1dry weight·h1(P < 0.001), and the higher doses of 0.6 and 1.0 mg·kg1prolactin reversed net water absorption to net water secretion of 2.20 ± 0.63 and 2.33 ± 0.89 mL·g1dry weight·h1, respectively (P < 0.001). The stimulatory effect of prolactin on water transport was completely abolished by reducing the perfusion rate from 1.0 mL·min1to zero. The stimulatory effect of prolactin on water secretion at perfusion rate of 1.0 mL·min1was also abolished when luminal [Na+] was reduced from 180 to 80 mM. We concluded that, unlike in the small intestine, calcium fluxes in the colon are not related to water transport and did not respond at all to prolactin. Water transport, on the other hand, was reversed from net absorption to secretion by prolactin. We propose that this prolactin-induced water secretion is probably mediated by recycling of luminal sodium in the vicinity of tight junctions.Key words: calcium fluxes, colon, perfusion technique, prolactin, water transport.
Calcium homeostasis in a clonal pituitary cell line of mouse corticotropes
Authors: Fiekers J F , Gelbspan D , Heppner T J
Published: April 2011

Calcium homeostasis was studied following a depolarization-induced transient increase in [Ca2+]iin single cells of the clonal pituitary cell line of corticotropes, AtT-20 cells. The KCl-induced increase in [Ca2+]iwas blocked in (i) extracellular calcium-deficient solutions, (ii) external cobalt (2.0 mM), (iii) cadmium (200 µM), and (iv) nifedipine (2.0 µM). The mean increase in [Ca2+]iin single cells in the presence of an uncoupler of mitochondrial function [carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, FCCP, 1 µM] was 54 ± 13 nM (n = 9). The increase in [Ca2+]iproduced by FCCP was greater either during or following a KCl-induced [Ca2+]iload. However, FCCP did not significantly alter the clearance of calcium during a KCl-induced rise in [Ca2+]i. Fifty percent of the cells responded to caffeine (10 mM) with an increase in [Ca2+]i(191 ± 24 nM; n = 21) above resting levels; this effect was blocked by ryanodine (10 µM). Thapsigargin (2 µM) and 2,5 di(-t-butyl)-1,4 hydroquinone (BuBHQ, 10 µM) produced increases in [Ca2+]i(47 ± 11 nM, n = 6 and 22 ± 4 nM, n = 8, respectively) that increased cell excitability. These results support a role for mitochondria and sarco-endoplasmic reticulum calcium stores in cytosolic [Ca2+]iregulation; however, none of these organelles are primarily responsible for the return of [Ca2+]ito resting levels following this KCl-induced [Ca2+]iload.Key words: calcium homeostasis, intracellular calcium stores, anterior pituitary cells, mitochondria.
Antiproliferative effect of brief exposure to cholera toxin in vascular smooth muscle cells: role of cAMP and protein kinase A
Authors: Thorin-Trescases Nathalie , Orlov Sergei N , Taurin Sébastien , Dulin Nickolai O , Allen Bruce G , deBlois Denis , Tremblay Johanne , Pshezhetsky Alexei V , Hamet Pavel
Published: April 2011

The effect of cholera toxin (CTX), an activator of the adenylate cyclase-coupled G protein αSsubunit, was studied on cultured vascular smooth muscle cell (VSMC) proliferation. Continuous exposure (48 h) to CTX as well as 2-min pretreatment of VSMC with CTX led to the same level of cAMP production, inhibition of DNA synthesis, and arrest in the G1phase without induction of necrosis or apoptosis in VSMC. Protein kinase A (PKA) activity in CTX-pretreated cells was transiently elevated by 3-fold after 3 h of incubation, whereas after 48 h it was reduced by 2-fold compared with baseline values without modulation of the expression of its catalytic α subunit. The PKA inhibitors H89 and KT 5720 did not protect VSMC from the antiproliferative effect of CTX. Two-dimensional electrophoresis was used to analyze the influence of CTX on protein phosphorylation. After 3 h of incubation of CTX-pretreated cells, we observed both newly-phosphorylated and dephosphorylated proteins (77 and 50 protein species, respectively). After 24 h of incubation, the number of phosphorylated proteins in CTX-treated cells was decreased to 39, whereas the number of dephosphorylated proteins was increased to 106. In conclusion, brief exposure to CTX leads to full-scale activation of cAMP signaling and evokes VSMC arrest in the G1phase.Key words: vascular smooth muscle, proliferation, cholera toxin, cAMP, protein kinase A.
Diminished molecular response to doxorubicin and loss of cardioprotective effect of dexrazoxane inEgr-1deficient female mice
Authors: Saadane Nacéra , Yue Ping , Alpert Lesley , Mitmaker Benjamin , Kirby Gordon M , Chalifour Lorraine E
Published: April 2011

Doxorubicin (DOX) and VP16 are DNA topoisomerase II inhibitors yet only DOX induces an irreversible cardiotoxicity, likely through DOX-induced oxidative stress. Egr-1 is overexpressed after many stimuli that increase oxidative stress in vitro and after DOX-injection into adult mice in vivo. To investigate Egr-1 function in the heart, we compared the molecular and histological responses of wild type (+/+) and Egr-1 deficient (/) female mice to saline, DOX, VP16, the cardioprotectant dexrazoxane (DZR), or DOX+DZR injection. DOX, and to a lesser extent VP16, induced characteristic increases in cardiac muscle and non-muscle genes typical of cardiac damage in +/+ mice, whereas only β-MHC and Sp1 were increased in / mice. DZR-alone treated +/+ mice showed increased cardiomyocyte transnuclear width without a change to the heart to body weight (HW/BW) ratio. However, DZR-alone treated / mice had an increased HW/BW, increased cardiomyocyte transnuclear width, and gene expression changes similar to DOX-injected +/+ mice. DZR pre-injection alleviated DOX-induced gene changes in +/+ mice; in DZR+DOX injected / mice the increases in cardiac and non-muscle gene expression were equal to, or exceeded that, detected after DOX-alone or DZR-alone injections. We conclude that Egr-1 is required for DOX-induced molecular changes and for DZR-mediated cardioprotection.Key words: mice, gene expression, doxorubicin, DNA topoisomerase II inhibitors, cardioprotection.
Endothelium-derived relaxing factors: A focus on endothelium-derived hyperpolarizing factor(s)
Authors: McGuire John J , Ding Hong , Triggle Chris R
Published: April 2011

Endothelium-derived hyperpolarizing factor (EDHF) is defined as the non-nitric oxide (NO) and non-prostacyclin (PGI2) substance that mediates endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells (VSMC). Although both NO and PGI2have been demonstrated to hyperpolarize VSMC by cGMP- and cAMP-dependent mechanisms, respectively, and in the case of NO by cGMP-independent mechanisms, a considerable body of evidence suggests that an additional cellular mechanism must exist that mediates EDH. Despite intensive investigation, there is no agreement as to the nature of the cellular processes that mediates the non-NO/PGI2mediated hyperpolarization. Epoxyeicosatrienoic acids (EET), an endogenous anandamide, a small increase in the extracellular concentration of K+, and electronic coupling via myoendothelial cell gap junctions have all been hypothesized as contributors to EDH. An attractive hypothesis is that EDH is mediated via both chemical and electrical transmissions, however, the contribution from chemical mediators versus electrical transmission varies in a tissue- and species-dependent manner, suggesting vessel-specific specialization. If this hypothesis proves to be correct then the potential exists for the development of vessel and organ-selective vasodilators. Because endothelium-dependent vasodilatation is dysfunctional in disease states (i.e., atherosclerosis), selective vasodilators may prove to be important therapeutic agents.Key words: endothelium, nitric oxide, potassium channels, hyperpolarization, gap junctions.