bluuebunny/crossref_metadata_2025 huggingface dataset:
Carotid–cardiac baroreflex and training status: significance of initial responsiveness
Authors: Savard G. K. , Lundie M. J.
Published: April 2011

The aim of this study was to demonstrate that within a population of healthy men (n = 15) of varying levels of aerobic fitness [Formula: see text], (i) there are high and low responders with respect to carotid–cardiac baroreflex responsiveness, despite similar baseline heart rates (HRs) both at rest and during dynamic exercise, and (ii) there is a weak association between this responsiveness and training status [Formula: see text] because of a large overlap in the responses between trained (endurance, ET) and untrained (UT) individuals. Baroreflex function curves were derived during supine rest for each subject by applying varying pressures around the neck in a beat-to-beat ramp (for 12 beats) of +40 to −60 mmHg (1 mmHg = 133.3 Pa). Subjects were divided into low (n = 8) and high (n = 7) responders on the basis of the magnitude of the maximal dynamic R–R interval (RRI) range of the baroreflex curve. Both bradycardic (percent slowing) and tachycardic (percent acceleration) components of the baroreflex curve, and peak sinus node responses (HR, RRI) to continuous neck suction (−60 mmHg) at rest and during exercise (cycling, 45% [Formula: see text]) were greater in high compared with low responders (p < 0.05), as assessed using both HR and RRI scales. When subjects were divided into ET and UT groups, both RRI range and maximal gain at rest were the only indices of baroreflex responsiveness that were different (p < 0.05) between the two groups, and a significant correlation was found between [Formula: see text] and RRI range (r2 = 0.497, p < 0.01); a lower resting HR in ET and mathematical skewing with the RRI scale could in part explain these findings. Taken together, these results emphasize that initial carotid–cardiac baroreflex responsiveness must be considered when assessing the effect of exercise training on baroreflex function.Key words: arterial baroreflex, bradycardia, parasympathetic, endurance training.
Renal and renin responses to furosemide in conscious lambs during postnatal maturation
Authors: Smith Francine G. , Abraham Jessica
Published: April 2011

Despite the widespread use of furosemide in the treatment of various fluid and electrolyte disorders in the preterm and term human infant and child, the physiological effects of this potent diuretic agent on renal function and renin release during postnatal maturation are poorly understood. To test the hypothesis that the renal and renin responses to furosemide are altered during postnatal maturation, experiments were carried out in conscious chronically instrumented newborn lambs (11 ± 3 days, n = 7) and older lambs (28 ± 3 days, n = 6), at least 5 days after surgery under halothane anesthesia for placement of catheters. Renal function and plasma renin activity (PRA) were measured for 1 h before and 2 h after intravenous injection of furosemide (2 mg/kg; 0.2 mL/kg) or vehicle (0.2 mL/kg). Glomerular filtration rate (GFR) decreased after furosemide administration to both groups of lambs. However, the time course of this decrease in GFR was different, occurring sooner in older lambs (30 min) than in newborns (90 min). GFR remained significantly decreased after 150 min in both age-groups. The natriuretic and diuretic responses to furosemide were similar in newborns and older iambs, peak diuretic and natriuretic responses occurring within 30 min. PRA increased dramatically in both age-groups after furosemide; the response was accentuated in newborns. After 2 h, PRA was still elevated in newborns but returned towards control levels in older lambs. These data demonstrate that both the GFR and renin responses to furosemide are altered during ontogeny.Key words: renal function, diuretic, blood volume, renin–angiotensin system, renal nerves, neonate, baroreflex.
Hormonal modulation of atrial natriuretic factor receptors in adrenal fasciculata cells from female rats
Authors: Mulay Shree , Vaillancourt Patrice , Omer Saeed , Varma Daya R.
Published: April 2011

We recently reported that the hormonal status of female rats modified atrial natriuretic factor (ANF) receptors and the aldosterone-suppressant activity of ANF in adrenal glomerulosa cells; here we investigated if this was also true for adrenal fasciculata cells. Adrenal fasciculata cells from animals in different hormonal states contained guanylate cyclase linked ANF-R1 receptors but not ANF-R2 (clearance) receptors. The concentration of ANF-R1 receptors in cells from intact virgin rats was insignificantly higher than in cells from 13- to 15-day pregnant rats and significantly higher than in cells from ovariectomized (OVX), OVX β-estradiol-treated, and OVX progesterone-treated rats. Under none of the hormonal states did ANF suppress adrenocorticotropic hormone (ACTH) stimulated corticosterone secretion. Data suggest that the interactions between ANF and ACTH on mineralocorticoid and glucocorticoid synthesis markedly differ.Key words: atrial natriuretic factor receptors, corticosterone, estrogen, progesterone, pregnancy.
Selective increase of rat lung cytochrome P450 1A1 dependent monooxygenase activity after acute sodium arsenite administration
Authors: Albores Arnulfo , Sinal Christopher J. , Bend John R. , Cherian M. George
Published: April 2011

Arsenic is a known pulmonary, hepatic, and skin carcinogen in humans and a known inducer of stress proteins. Consequently, the ability of arsenite (As3+) to modulate isozyme-selective cytochrome P450 (P450) dependent monooxygenase activities was investigated in microsomes prepared from lung, liver, and kidney of male, adult Sprague–Dawley rats treated subcutaneously (s.c.) with sodium arsenite (75 μmol/kg body weight) 24 h before death. In the lung, the activity of P450 1A1 catalyzed 7-ethoxyresorufin O-deethylation (ERFD) was markedly (approximately 5-fold) increased in treated versus control rats, whereas the activity of P450 2B catalyzed 7-pentoxyresorufin O-depentylation (PRFD) was unchanged. Pulmonary ERF activity remained elevated for at least 48 h after As3+treatment. In contrast, As3+inhibited hepatic microsomal ERFD and PRFD activity by approximately 20 and 35%, respectively, 24 h after treatment. ERFD activity was also decreased in kidney microsomes of As3+-treated rats, but the inhibition was greater than in liver (50 vs. 35%) 24 h after injection. These effects are almost certainly not due to a direct action of As3+on P450-dependent catalysis, as in vitro addition of sodium As3+at concentrations up to 1 mM had no effect on ERFD activity of control rat lung microsomes. In addition, pretreatment of rats with Zn (153 μmol∙kg−1∙day−1for 2 days, s.c.) had no effect on control or As3+-mediated changes in P450-dependent ERFD activity of rat lung or kidney microsomes. These results demonstrate that As3+is an isozyme-selective modulator of P450 monooxygenase activity (i.e., significant increase of P450 1A1 catalyzed activity but not P450 2B catalyzed activity) in rat lung. In contrast, ERFD activity was significantly inhibited in both liver and kidney of the same As3+-treated rats.Key words: microsomal cytochrome P450, arsenite, oxidative stress, induction, liver, lung, kidney, monooxygenase activity.
Species differences in the physical and transport properties of airway secretions
Authors: Tomkiewicz Robert P. , Albers Gary M. , Ramirez Oscar E. , Rubin Bruce K. , Sanctis George T. De , King Malcolm
Published: April 2011

The clearance of airway secretions is vital in protecting the mammalian lung from pollution and infection. Diverse animal models have been used to study lung diseases associated with impaired secretion clearance. The extrapolation of data from animal models to humans is based on the assumption that there are structural and functional similarities in the airway epithelium and secretions. This manuscript reviews regulation of mucus secretion as well as the physical and transport properties of respiratory mucus. As tracheal size increases, the rigidity of airway secretions decreases, and rigidity is inversely correlated with mucociliary transportability. These differences are placed in the context of previously reported species and regional differences in transepithelial potential difference and the tracheobronchial epithelial cell population. Tracheal mucus transport velocity varies with the species studied and has been shown to positively correlate with tracheal surface area. A progressive increase in the rate of mucus transport from the small to the large airways has also been reported. The reduction in mucus rigidity from small to large airways could be one of the mechanisms responsible for velocity gradients, which facilitate mucociliary transport. Because airway dimensions, rather than anatomic level of the airway, may better predict epithelial secretory response, studies to assess the physiologic responses in human airways require the use of an animal model with a similar-sized airway.Key words: mucus, airways, animal models, lung disease.
Sense of muscular effort and somesthetic afferent information in humans
Authors: Sanes Jerome N. , Shadmehr Reza
Published: April 2011

Laboratory and clinical observations of patients with a large-fiber somatic sensory neuropathy indicate a dramatic inability of these patients to set accurate tonic or phasic levels of muscle activity needed to maintain static postures and to reproduce simple movements. These observations suggest that somatic sensation contributes to sensations of motor output, previously thought to be mediated by central mechanisms of corollary discharge. We review data describing psychophysical performance on weight-matching tasks and discuss new experiments on reaching tasks done by patients with a large-fiber sensory neuropathy and normal controls. In combination, the data show that patients with peripheral sensory deficits exhibit an impaired sense of muscular effort and the consequences of active movement. In addition, the data on weight matching indicate that the basis of disrupted effort sense relates to an inability to correlate psychophysical decisions with concomitant muscle activity. In new experiments, accuracy to match actively achieved arm end points by pointing was decreased in patients with large-fiber sensory neuropathy. The collective results suggest that appreciation of motor output is mediated in part by peripheral return from somatic sensory afferent systems.Key words: muscular effort, sensory neuropathy, motor control, human.
Is proprioception important for the timing of motor activities?
Authors: LaRue Jacues , Bard Chantal , Fleury Michelle , Teasdale Normand , Paillard Jacques , Forget Robert , Lamarre Yves
Published: April 2011

This study tested whether a deafferented patient demonstrates impaired timing ability compared with four control subjects. By comparing normal subjects with the deafferented patient, some insight was expected on the importance of proprioception in timing of motor behavior. The protocol was set to enhance the strategy of the subjects in using feedbacks. Subjects had to synchronize finger taps with a sound produced at regular intervals. Once synchronized, the bips were muted and the subjects had to continue the tapping at the same pace. Interresponse interval (IRI) variability was measured under two feedback conditions: with and without vision and auditory feedback. The Wing and Kristofferson model (A.M. Wing and A.B. Kristofferson. Percept. Psychophys. 13(3): 455–460. 1973) was used to segment IRI variance into separate components: a central clock and a peripheral motor delay. When the deafferented patient saw and heard the outcome of her tapping movements, there was a greater variability in successive intervals between taps than when vison and hearing were blocked. We interpret this variability as indicating that the subject used auditory and visual feedback to maintain a correct overall rhythm. The patient may easily substitute visual and (or) auditory feedback for her defective proprioception for movement timing. However, this substitution proved to be inefficient in the limited training period provided in this experiment. The results suggest that the proprioceptive contribution to the time-keeping mechanism presumably depends on the presence of an efference copy signal.Key words: tapping, Wing and Kristofferson model, repetitive movements, synchronization, efference copy.
Decreased vascular contractile and inositol phosphate responses in portal hypertensive rats
Authors: Huang Yi-Tsau , Hong Chuang-Ye , Yu Pi-Chin , Lee Ming-Fang , Yang May C. M. , Lin Han-Chieh
Published: April 2011

The purpose of this study was to investigate the vascular contractile and inositol phosphate responses in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL) in Sprague–Dawley rats. Sham-operated rats served as controls. Pressures, vasoconstrictor responses, and inositol phosphate responses were determined at 14 days after surgery. The portal venous pressure was significantly higher, while systemic arterial pressure and heart rate were lower, in PVL rats. Dose-dependent contractile responses were observed for both norepinephrine (1 × 10−8– 3 × 10−6 M) and vasopressin (3 × 10−10– 3 × 10−8 M) in the tail artery of both groups. The contractile response to norepinephrine was significantly decreased in PVL rats compared with controls at all doses. The contractile response to vasopressin was significantly decreased in PVL rats at higher doses. After myo-[3H]inositol incorporation in tail artery, the levels of3H-labelled phosphatidylinositols (cpm/mg) were similar between the two groups. Norepinephrine (10−7– 10−5 M) and vasopressin (10−10– 10−8 M) dose dependently stimulated the3H-labelled inositol phosphate production in the tail artery of both PVL and sham-operated rats. However, the response was significantly lower in PVL rats. The results suggested that the attenuation of vascular contractile responses in portal hypertension was reflected in the phosphoinositide messenger system.Key words: portal hypertension, inositol phosphates, phosphoinositide, tail artery, contractile response.
Proliferation and progesterone production of ovine luteal cells from several stages of the estrous cycle: effects of fibroblast growth factors and luteinizing hormone
Authors: Grazul-Bilska A. T. , Redmer D. A. , Jablonka-Shariff A. , Biondini M. E. , Reynolds L. P.
Published: April 2011

This study was conducted to evaluate the effects of fibroblast growth factor 1 (FGF-1), fibroblast growth factor 2 (FGF-2), or luteinizing hormone (LH) on proliferation and progesterone secretion of ovine luteal cells from days 5, 10, or 15 after estrus (estrus = day 0; n = 4 or 5 ewes/day). After enzymatic dispersion, luteal cells were incubated in the presence or absence of various doses of FGF-1, FGF-2, LH, or fetal bovine serum (FBS) (positive control) in serum-free media for 7 days in 24-well plates. Cells were counted on day 7 of culture and media analyzed for progesterone concentration. For all treatments, maximal effects (Emax) and dissociation constants (KD) were calculated. In addition, luteal cells were cultured in eight-chamber slides and treated as above, but on day 7 of culture cells were fixed and stained for the presence of 3β-hydroxy-Δ5-steroid dehydrogenase (3βHSD). The number of steroidogenic (3βHSD positive) cells per unit area was counted for control cultures (no treatment) and cultures treated with the most effective doses of FGF-1, FGF-2, LH, or FBS in proliferation and (or) progesterone assays. FGF-1, FGF-2, and FBS stimulated (p < 0.05) proliferation of luteal cells from all stages of luteal development in a dose-dependent manner. In addition, LH increased (p < 0.01) the number of 3βHSD-positive cells across all stages of luteal development. Moreover, LH and FBS increased (p < 0.05) progesterone secretion by luteal cells from all stages in a dose-responsive manner, but the effects of FGF-1 and FGF-2 were variable. For proliferation, the Emax of all factors was greatest (p < 0.01) on day 5, whereas the KD values were similar across days of the estrous cycle. For progesterone production, the Emax and KD of LH and FBS were similar and did not differ across the estrous cycle. These data demonstrate that luteal cells from the early luteal phase of the estrous cycle exhibit the greatest ability to proliferate and (or) increase their progesterone secretion in response to FGF-1, FGF-2, LH, or FBS. In addition, although LH does not affect the total number of luteal cells in culture, it does increase the number of steroidogenic cells. These data indicate that in addition to LH, fibroblast growth factors may be involved in regulation of luteal growth and differentiation in ewes.Key words: proliferation, progesterone, fibroblast growth factor, luteinizing hormone, corpora lutea, ewe, dose–response.
Pathophysiology of smooth muscle in hypertension
Authors: Lee Robert M. K. W. , Owens Gary K. , Scott-Burden Timothy , Head Richard J. , Mulvany Michael J. , Schiffrin Ernesto L.
Published: April 2011

Structural changes of the arteries in hypertension are determined by the unique genetics of the animals and by various growth promoters and growth inhibitors. Vascular smooth muscle cell growth promoting factors include fibroblast growth factor, platelet-derived growth factor, and vasoactive peptides such as norepinephrine, angiotensin II, and endothelin. Endothelial cells secrete three types of growth inhibiting factors. These are heparin – heparan sulfate, transforming growth factor β, and nitric oxide. The effect of sympathetic innervation on vascular growth is probably dependent on its interaction with the rennin–angiotensin system. In the mesenteric vascular bed, the elevated resistance in the arterial system is present in both the macroarteries and in the more distal microarteries and veins. Changes in resistance arteries include hypertrophy and reduction in outer diameter (remodelling). In the resistance arteries from human essential hypertensives, remodelling is the predominant finding. Long-term treatment with an angiotensin I converting enzyme inhibitor but not with a β-blocker was effective in reversing this type of vascular change. Studies have suggested that in addition to angiotensin II, endothelin may play a role in vascular remodelling of resistance arteries.Key words: hypertension, vascular, remodelling, smooth muscle, growth factors.
Mitochondrial biogenesis during pressure overload induced cardiac hypertrophy in adult rats
Authors: Nishio Mary L. , Ornatsky Olga I. , Craig Elaine E. , Hood David A.
Published: April 2011

Existing literature provides an equivocal picture of the behavior of mitochondrial synthesis during the time course of cardiac hypertrophy. Therefore, we examined the effect of cardiac hypertrophy on mitochondrial cytochrome c oxidase (CYTOX) activity, the content of CYTOX subunit VIc mRNA, and the expression of molecular chaperones. Adult male Sprague–Dawley rats were subjected to either abdominal aortic constriction to induce pressure overload (PO) or a sham operation (SH). Animals were studied 2, 4, 7, 14, 21, or 28 days after surgery. Aortic constriction resulted in a significant elevation in arterial pressure by 4 days after surgery. Significant (p < 0.05) hypertrophy was attained by 4 days and was stabilized at 37% between 7 and 28 days. CYTOX activity (U/g) did not differ significantly between PO and SH animals at either early (<7 days) or later time points, indicating that mitochondrial content increased in proportion to adaptive cellular hypertrophic growth. The concentration of the molecular chaperones HSP60 and GRP75 involved in mitochondrial protein import did not change with PO treatment. The levels of mRNAs encoding both CYTOX subunit VIc and HSP60 remained constant, in proportion to cardiac growth. This suggests that the accelerated synthesis of CYTOX and HSP60 during cardiac hypertrophy is regulated transcriptionally. The data help to resolve the controversy in the literature regarding mitochondrial biogenesis during moderate, stable cardiac hypertrophy, and they indirectly indicate that proportional mitochondrial synthesis relative to cellular hypertrophy is regulated at the transcriptional level.Key words: hypertension, cytochrome c oxidase, mRNA, cytochrome c oxidase subunits, aortic constriction, heat shock proteins, molecular chaperones.
Alterations in neurokinin 1 receptor gene expression in models of pain and inflammation
Authors: Krause J. E. , Dimaggio D. A. , McCarson K. E.
Published: April 2011

Substance P and the related tachykinin peptides are involved in inflammatory processes and in the transmission of sensory nociceptive information. In this article we review the evidence implicating substance P and the neurokinin 1 (NK1) receptor in arthritic disease. We also provide preliminary evidence demonstrating that cultured synoviocytes from a patient with rheumatoid arthritis express NK1receptor mRNA that can be downregulated by tumor necrosis factor α, whereas synoviocytes from a normal patient do not express detectable NK1receptor mRNA or protein. Data are also presented summarizing recent studies on nociception-induced increases in sensory ganglia of levels of mRNA encoding substance P and increases in dorsal horn NK1receptor mRNA levels. Morphine pretreatment blocked the increases in dorsal horn NK1receptor mRNA levels but did not block the nociception-induced substance P encoding mRNA levels in sensory ganglia. These results are discussed with reference to mechanisms that may regulate substance P turnover and NK1receptor sensitivity in models of pain and inflammation.Key words: substance P, dorsal root ganglia, G-protein-coupled receptor, Formalin test, synovium.
Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A
Authors: Qtsuka M. , Yoshioka K. , Yanagisawa M. , Suzuki H. , Zhao F.-Y. , Guo J.-Z. , Hosoki R. , Kurihara T.
Published: April 2011

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.Key words: substance P, neurokinin A, neurotransmitter, tachykinin antagonist, spinal cord.
Comparative immunohistochemical distribution of amylin-like and calcitonin gene related peptide like immunoreactivity in the rat central nervous system
Authors: Skofitseh Gerhard , Gubisch Wolfgang , Wimalawansa Sunil J. , Jacobowitz David M.
Published: April 2011

Using the indirect immunofluorescence method with a polyclonal antiserum raised in rabbits and directed against amylin (AMY), we have investigated the distribution of AMY-like immunoreactivity (-ir) throughout the central nervous system of the rat. The widespread distribution of AMY-ir was much more abundant than that previously reported for calcitonin gene related peptide (CGRP) immunoreactivity. In most brain areas there was no overlap between AMY- and CGRP-ir cell body groupings, with the exception of the motor nuclei of the hindbrain and spinal cord, which were found to contain large numbers of AMY- and CGRP-immunoreactive cell bodies. Areas with a moderate to dense appearance of AMY-ir were the rhinencephalon, the nucleus of the diagonal band, the magnocellular, dorso- and ventro-medial and mammillary nuclei of the hypothalamus, the habenula, the compact part of the substantia nigra, the ruber and pontine nuclei, and the inferior olive and the cerebellar nuclei. The widespread immunohistochemical distribution of AMY-ir in the rat brain is in partial agreement with the distribution of AMY-binding sites.Key words: calcitonin gene related peptide, amylin, central nervous system, immunohistochemistry, rat.
Calcitonin gene related peptide as inhibitory neurotransmitter in the ureter
Authors: Maggi C. A. , Giuliani S. , Meini S. , Santicioli P.
Published: April 2011

A dense plexus of calcitonin gene related peptide (CGRP) containing nerve fibres is present in the mammalian ureter, from which CGRP is released by depolarizing stimuli, including chemicals normally present in the urine. CGRP exerts a profound, receptor-mediated, inhibitory effect on the evoked motility of the ureter by suppressing latent pacemakers in the smooth muscle. This effect is largely glibenclamide sensitive, indicating the activation of potassium (K) channels in its genesis. Electrical stimulation of intramural nerves in the guinea-pig ureter produces a transient membrane hyperpolarization, which is blocked by glibenclamide or by capsaicin pretreatment, enhanced in a low-K medium, and inhibited by a CGRP receptor antagonist. Thus endogenous CGRP acts as a neurotransmitter K channel opener in the ureter. The refractory period of the guinea-pig ureter is markedly and similarly reduced by capsaicin pretreatment or administration of a CGRP receptor antagonist, indicating that endogenous CGRP can modulate the maximal frequency of ureteral peristalsis. Using a three-chamber organ bath that enabled the separate perfusion of the renal, middle, and bladder regions of the organ, evidence was obtained that CGRP blocks propagation of impulses along the ureter through a glibenclamide-sensitive mechanism. These findings indicate a role of CGRP in the local regulation of ureteral motility and peristalsis.Key words: guinea-pig ureter, calcitonin gene related peptide, sensory nerves, glibenclamide-sensitive potassium channels.
Plasticity of calcitonin gene related peptide neurotransmission in the spinal cord during peripheral inflammation
Authors: Seybold V. S. , Galeazza M. T. , Garry M. G. , Hargreaves K. M.
Published: April 2011

Injection of complete Freund's adjuvant (CFA; 75 μL) into the plantar surface of the hind paw of the rat results in a mild inflammation that lasts for several days and is accompanied by hyperalgesia. Multiple components of calcitonin gene related peptide (CGRP) neurotransmission in the spinal cord are altered during the course of this peripheral inflammation. The content of immunoreactive (i) CGRP in the dorsal horn of the spinal cord, where primary afferent neurons terminate, is significantly decreased within 2 days after injection of CFA but increases to a level greater than that of the control at 8 days. The early decrease in iCGRP in the spinal cord suggests that the release of CGRP from primary afferent neurons is increased during the period of maximal hyperalgesia that accompanies peripheral inflammation. Changes in the mRNA for CGRP suggest that the increase in spinal content of iCGRP is due to an increase in synthesis of the peptide as the level of mRNA for CGRP is increased from 2 to 8 days after injection of CFA. Despite the decrease in the content of iCGRP in the spinal cord, there is no apparent decrease in the amount of iCGRP that can be released from the dorsal spinal cord by capsaicin; in fact, capsaicin-evoked release is increased at 4 days. Measurements of the binding of 125I-labelled CGRP in the dorsal spinal cord indicate that high affinity binding sites for CGRP are downregulated at 4 days after injection of CFA. In total, these data support the hypothesis that the activity of CGRP-containing primary afferent neurons is increased during peripheral inflammation. CGRP released from primary afferent neurons in the spinal cord may contribute to cellular changes that accompany peripheral inflammation.Key words: calcitonin gene related peptide, dorsal root ganglion, hyperalgesia, inflammation, spinal cord.
Binding sites for islet amyloid polypeptide in mammalian lung: species variation and effects on adenylyl cyclase
Authors: Bhogal Ranjev , Smith David M. , Owji Ali A. , Bloom Stephen R.
Published: April 2011

Islet amyloid polypeptide (IAPP) and calcitonin gene related peptide (CGRP) share a 47% sequence homology. IAPP can interact with adenylyl cyclase coupled CGRP receptors. We have examined [125I]IAPP binding in mouse, pig, and guinea pig lung membranes in competition with IAPP, CGRP, and CGRP(8–37). Three types of site were shown by order of potency: (i) mouse, IAPP > CGRP(8–37) [Formula: see text] CGRP; (ii) pig, CGRP > IAPP > CGRP(8–37); and (iii) guinea pig, CGRP = IAPP = CGRP(8–37). Chemical cross-linking of [125I]IAPP and [125I]CGRP binding sites in lung demonstrated that both sites had similar molecular weights in any one species but differed across species, i.e., mouse Mr = 70 000 and 98 000; pig Mr = 68 000, 56 000, and 47 000; and guinea pig Mr = 106 000 and 56 000. Adenylyl cyclase activity was stimulated by forskolin and AlCl3–NaF in rat, mouse, pig, and guinea pig membranes. Only in mouse and pig were CGRP and IAPP able to stimulate adenylyl cyclase activity. In mouse lung CGRP and IAPP stimulated adenylyl cyclase activity with EC50 values of 642 ± 222 nM (n = 4) and 325 ± 115 nM (n = 4), respectively. In pig lung membranes EC50 values were 5.7 ± 0.3 nM (n = 4) for CGRP and 1230 ± 1130 nM (n = 4) for IAPP. Thus IAPP either did not stimulate adenylyl cyclase activity in these lung membranes or did so with a low potency.Key words: islet amyloid polypeptide, amylin, calcitonin gene related peptide, lung, receptors.
Regulation of postsynaptic responses by calcitonin gene related peptide and ATP at developing neuromuscular junctions
Authors: Lu Bai , Fu Wen-Mei
Published: April 2011

Neuronal factors co-released with neurotransmitters may play an important role in synapse development and function. Calcitonin gene related peptide (CGRP) and adenosine 5′-triphosphate (ATP), two principal neuromodulators present in the motor nerve terminals, were studied for their roles and mechanisms during early development of neuromuscular synapses in Xenopus nerve–muscle co-cultures. CGRP treatment increased the decay time and amplitude of spontaneous synaptic currents (SSCs) recorded from innervated myocytes, without affecting SSC frequency, suggesting a postsynaptic mechanism. ATP also increased the SSC amplitude and decay time. In addition, ATP was shown to potentiate the responses of isolated myocytes to iontophoretically applied acetylcholine (ACh). Single-channel recording from isolated myocytes showed that both CGRP and ATP specifically increased the open time of embryonic-type, low-conductance ACh channels. Pharmacological experiments suggest that the CGRP actions were mediated by cAMP-dependent protein kinase (PKA), while ATP exerted its effects by binding to P2 purinoceptors and thereby activating protein kinase C (PKC). Moreover, the effects of CGRP and ATP on ACh channel activity were restricted to immature myocytes. Taken together, these results suggest that endogenous CGRP and ATP co-released with ACh from the nerve terminal may promote synaptic development by potentiating postsynaptic ACh channel activity during the early phase of synaptogenesis.Key words: acetylcholine receptor, protein kinase A, protein kinase C, Xenopus, synaptogenesis.
Acute effect of prolactin on active calcium absorption in rats
Authors: Krishnamra Nateetip , Taweerathitam Premthip
Published: April 2011

Acute effect of prolactin on active calcium absorption was investigated by using the in vitro everted gut sac technique. An intraperitoneal administration of a pharmacological dose of 0.02 mg prolactin/100 g body weight 5 or 10 min before the in vitro experiment significantly increased the active calcium transport (represented by the ratio of serosal to mucosal 45Ca concentration) only in the duodenum, not in other segments. This prolactin-induced duodenal active transport was seen in 8-week-old sexually mature rats but not in 3-week-old weaned, 5-week-old young, or > 15-month-old rats. Enhanced apical uptake of 45Ca in 2 min by the oil-filled everted duodenal sac from rats that received prolactin 5 and 10 min prior to the experiment further supported the speculation that prolactin could acutely alter the duodenal epithelial handling of calcium.Key words: active transport, calcium, everted gut sac, intestinal absorption, prolactin.
Temporal constraints in associative synaptic plasticity in hippocampus and neocortex
Authors: Debanne Dominique , Shulz Daniel E. , Frégnac Yves
Published: April 2011

We present comparative experimental evidence for the induction of synaptic potentiation and depression in organotypic cultures of hippocampus and in visual cortex in vitro and in vivo. The effects of associative pairings on the efficacy of synaptic transmission are analyzed as a function of the temporal delay between presynaptic activity and post-synaptic changes imposed in membrane potential. Synchronous association at a low temporal frequency (<0.5 Hz) between presynaptic input and postsynaptic depolarization resulted in homosynaptic potentiation of functionally identified postsynaptic potentials in the three types of preparation. Synchronous pairing of afferent activity with hyperpolarization of the postsynaptic cell resulted in homosynaptic depression in visual cortex in vivo and in vitro. An associative form of depression was induced in hippocampus when the test input was followed repeatedly with a fixed-delay postsynaptic depolarization imposed either by intracellular current injection or synaptically. The latter process might play a significant role in heterosynaptic plasticity in visual cortex in vivo and in vitro, if it is assumed that associative depression still operates in visual cortex a few seconds after the initial surge of calcium in the postsynaptic cell. We conclude that the precise timing between presynaptic activity and polarization changes in postsynaptic membrane potential up- and down-regulates the efficacy of active pathways.Key words: synaptic potentiation, synaptic depression, asynchrony, covariance, supervised learning.
Spatial reciprocity of connections between areas 17 and 18 in the cat
Authors: Salin P. A. , Kennedy H. , Bullier J.
Published: April 2011

We examined whether the interconnections between areas 17 and 18 are spatially reciprocal, i.e., whether a column of cells in area 17 receives from the same region of area 18 as it sends projections to, and vice versa. We addressed this question by making side by side injections of retrograde fluorescent tracers in area 18, calculating the convergence and divergence of the connections from area 17 to 18. We compared these values with previously reported values of divergence and convergence of the projections from area 18 to area 17. The results demonstrate that there is a good match between the convergence and divergence of the area 17 to area 18 connection and, respectively, the divergence and convergence of the reverse connection. We confirmed directly the spatial reciprocity by injecting simultaneously in area 17 a retrograde and an anterograde tracer and by analyzing quantitatively the density of anterograde and retrograde labeling across the surface of area 18. There was an excellent match between the density maps of retrogradely labeled cells and anterogradely labeled axon terminals in area 18. Connections between areas 17 and 18 therefore exhibit large degrees of convergence and divergence and are spatially reciprocal. Thus, a given column of cells within one of these two areas is reciprocally interconnected with a large region of the opposite area. Such an organization may provide the basis for synchronization of firing of neurons across these two areas, as revealed by cross-correlation studies.Key words: double labeling, fluorescent tracers, retrograde and anterograde tracers, convergence and divergence.
Plasticity following neonatal visual cortex damage in cats
Authors: Spear Peter D.
Published: April 2011

We have used the cat visual system as a model system to investigate how remaining areas of the brain are able to take over functions that are lost following brain damage and why neonates show better behavioral recovery than adults. Anatomical studies with both anterograde and retrograde tracing methods reveal an increased projection from retina through thalamus to the posteromedial lateral suprasylvian (PMLS) extrastriate visual area of cortex in the damaged hemisphere of cats with a neonatal visual cortex (areas 17, 18, and 19; VC) lesion. No such enhanced projection is seen after an adult lesion. In addition, single-cell neurophysiological studies indicate that physiological compensation is present in PMLS cortex after a neonatal VC lesion but not after an adult lesion. The physiological compensation replaces (or maintains) properties that are characteristic of PMLS neurons; there is little or no improvement to replace the superior spatial properties of striate cortex (or areas 18 or 19) neurons that were lost. Immunohistochemical studies of the possible roles of neuronal growth factors in the compensation indicate that low- and high-affinity receptors are present that would allow several neurotrophins to influence the normal retina throughout life. Furthermore, these receptors are upregulated transneuronally following neonatal VC damage and thus could play a role in lesion-induced changes in the retina and its central projections. Ongoing studies are continuing to examine the presence of neurotrophins and their receptors in the retina and brain during normal development and after VC damage. In addition, studies of the effects of administering neuronal growth factors are underway to determine whether compensation for VC damage can be improved in neonates or even be produced in adults.Key words: visual cortex, neural plasticity, brain damage, neurotrophic substances, neonatal lesion.
Generation of slow wave type action potentials in the mouse small intestine involves a non-L-type calcium channel
Authors: Malysz John , Richardsons David , Farraway Laura , Huizinga Jan D. , Christen Marie-Odile
Published: April 2011

Intrinsic electrical activities in various isolated segments of the mouse small intestine were recorded (i) to characterize action potential generation and (ii) to obtain a profile on the ion channels involved in initiating the slow wave type action potentials (slow waves). Gradients in slow wave frequency, resting membrane potential, and occurrence of spiking activity were found, with the proximal intestine exhibiting the highest frequency, the most hyperpolarized cell membrane, and the greatest occurrence of spikes. The slow waves were only partially sensitive to L-type calcium channel blockers. Nifedipine, verapamil, and pinaverium bromide abolished spikes that occurred on the plateau phase of the slow waves in all tissues. The activity that remained in the presence of L-type calcium channel blockers, the upstroke potential, retained a similar amplitude to the original slow wave and was of identical frequency. The upstroke potential was not sensitive to a reduction in extracellular chloride or to the sodium channel blockers tetrodotoxin and mexiletine. Abolishment of the Na+ gradient by removal of 120 mM extracellular Na+ reduced the upstroke potential frequency by 13–18% and its amplitude by 50–70% in the ileum. The amplitude was similarly reduced by Ni2+ (up to 5 mM), and by flufenamic acid (100 μM), a nonspecific cation and chloride channel blocker. Gadolinium, a nonspecific blocker of cation and stretch-activated channels, had no effect. Throughout these pharmacological manipulations, a robust oscillation remained at 5–10 mV. This oscillation likely reflects pacemaker activity. It was rapidly abolished by removal of extracellular calcium but not affected by L-type calcium channel blockers. In summary, the mouse small intestine has been established as a model for research into slow wave generation and electrical pacemaker activity. The upstroke part of the slow wave has two components, the pacemaker component involves a non-L-type calcium channel.Key words: slow wave, pacemaker, calcium channel, pinaverium, smooth muscle.
Comparative studies on differential inhibition of the rennin–angiotensin system in the anesthetized guinea pig
Authors: Duan J. , Jaramillo J. , Jung G. L. , McLeod A. L. , Fernandas B. H. , Mathis D.
Published: April 2011

The present study compares the hemodynamic effects and mechanisms of action of angiotensin II (AngII) antagonists, angiotensin converting enzyme (ACE) inhibitors, and renin inhibitors in the guinea pig, an animal with high similarity to primates in terms of in vitro and in vivo responses to several human renin inhibitors. Animals were anesthetized with urethane and ketamine. The carotid artery was catheterized for monitoring blood pressure and heart rate. After 30 min stabilization, drug (or vehicle) effects were monitored for 1 h following each increasing dose (i.v. bolus injection). Drugs tested include losartan, an AngII receptor antagonist; two renin inhibitors, BILA 2157 BS and PD-134672; and captopril, an ACE inhibitor. All drugs dose dependency decreased blood pressure. Diastolic blood pressure was reduced more than systolic blood pressure, suggestive of vasodilation. The maximum decrease (32 ± 6%, p < 0.05 vs. vehicle) in mean arterial blood pressure (MABP) by losartan was achieved with a dose of 1 mg/kg. A similar decrease in MABP was observed with renin inhibitors at a dose of 3 mg/kg, without affecting heart rate. A further increase in the dose of renin inhibitors (6 mg/kg) decreased not only blood pressure but also heart rate. Captopril decreased MABP with a maximum of 48 ± 3% (p < 0.05 vs. vehicle, losartan, and PD-134672). In the presence of HOE-140, a bradykinin antagonist, the MABP decrease by captopril was only 35 ± 4%, (p < 0.05 vs. captopril alone). Bilateral nephrectomy reduced the peak MABP effect of PD-134672 by 67%, while the effects of captopril on MABP were affected to a lesser degree (57%). Therefore, captopril remains more effective in reducing MABP (p < 0.05 vs. that of PD-134672). These results suggest that renin inhibitors and AngII antagonists act more specifically on the rennin–angiotensin system cascade, while captopril acts partially by a bradykinin-dependent mechanism. The small animal model described provides a novel tool for the comparative pharmacologic assessment of different rennin–angiotensin system inhibitors.Key words: blood pressure, guinea pig, rennin–angiotensin system, rennin–angiotensin system inhibition.
Detection of sarcoma virus family tyrosine kinase activity in coronary arterial tissue
Authors: Laniyonu Adebayo , Eto Seiji , Wang Jerry H. , Hollenberg Morley D.
Published: April 2011

We have observed that the tyrosine kinase inhibitors genistein and tyrphostin can selectively block angiotensin II mediated and vasopressin-mediated contractions in porcine coronary arterial strips, without affecting the action of acetylcholine. Therefore, we assessed the presence of tyrosine kinase activity in the porcine coronary artery tissue, using an assay specific for sarcoma virus (src) related tyrosine kinases. In both membrane and cytosolic fractions of porcine coronary artery, we detected src-related tyrosine kinase activity that could be inhibited by both genistein and tyrphostin. The tyrosine kinase activity in membrane extracts was separated into two peaks by sequential chromatography on hydroxylapatite and Mono-Q columns. Protein in both peaks exhibited Western blot cross-reactivity with anti-src antibodies and contained tyrosine kinase activity that was inhibited by genistein and tyrphostin. We conclude that porcine coronary artery tissue contains src-related tyrosine kinase activity. However, because of the comparatively low sensitivity of the isolated src kinase activity towards genistein and tyrphostin, compared with the much higher sensitivity of the contractile response to these inhibitors, a direct role for c-src in the regulation of contractions elicited by agonists such as angiotensin II and arginine vasopressin cannot yet be assigned.Key words: tyrosine kinase, genistein, tyrphostin, coronary artery, angiotensin II, vasopressin.
Effect of prolonged catecholamine infusion on heart rate, blood pressure, breathing, and growth in fetal sheep
Authors: Bocking A. D. , White S. E. , Kent S. , Fraher L. , Man V. K. M. , Rundle H. , Hooper S. B.
Published: April 2011

Norepinephrine and epinephrine were infused into fetal sheep for 24 h to compare the effects on fetal heart rate, blood pressure, breathing movements, and tissue growth with those of prolonged reductions in uterine blood flow. Norepinephrine concentrations increased (p < 0.01) from 871 ± 71 to 6831 ± 1090 pg/mL (2 h) with norepinephrine infusion, and epinephrine concentrations increased from 310 ± 95 to 1424 ± 288 pg/mL (2 h) with epinephrine infusion. Fetal pH decreased (p < 0.01) from 7.37 ± 0.01 to 7.29 ± 0.02 at 0.5 h of the norepinephrine infusion and returned to control values by 2 h, whereas fetal lactate concentrations increased (p < 0.05) from 1.6 ± 0.2 to 4.6 ± 1.0 mmol/L at 2 h and remained elevated for 12 h. Lactate concentrations also increased with epinephrine infusion. Fetal heart rate increased (p < 0.05) from 176 ± 5 to 246 ± 6 and 220 ± 6 beats/min in the 1st h of norepinephrine and epinephrine infusions, respectively, with a subsequent decline. Fetal blood pressure increased (p < 0.05) from 43 ± 3 and 40 ± 2 to 53 ± 3 and 47 ± 2 mmHg (1 mmHg = 133.3 Pa) during the 1st h of norepinephrine and epinephrine infusions, respectively, remaining elevated for 24 h. Fetal body weights were not different between the groups of animals, although liver/body weight ratio was less (p < 0.05) in epinephrine-infused fetuses (0.030 ± 0.001) compared with vehicle-infused animals (0.036 ± 0.002). There was no change in DNA synthesis rate in any of the fetal organs, despite changes in organ-specific DNA and protein content. Our results indicate that the changes in fetal cardiovascular and behavioural function, as well as tissue growth, that occur with prolonged reductions in uterine blood flow are not mediated solely by elevated circulating catecholamine concentrations.Key words: fetal physiology, catecholamines, pregnancy.