bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional integrity of intrinsic cardiac nerves located over an acute transmural myocardial infarction
Authors: Janes R. D. , Johnstone D. E. , Armour J. A.
Published: April 2011

Acute transmural myocardial infarction has been reported to functionally denervate the normal myocardium distal to the infarcted zone by interrupting neurotransmission in axons coursing in the subepicardial region of the myocardial necrosis. To directly investigate the viability of such neurotransmission, the effects of acute transmural myocardial infarction on conduction in the intrinsic cardiac nerves overlying and distal to an experimentally induced acute transmural myocardial infarction were studied. In eight dogs, during control states electrical stimulation of the epicardium adjacent to a coronary artery produced compound action potentials in the more cranially located cardiopulmonary nerves. Thereafter, in four dogs an acute transmural myocardial infarction was produced by injecting rapidly hardening latex into a major diagonal branch of the left anterior descending coronary artery. Epicardial stimulation over the infarct, as well as proximal or distal to it, produced compound action potentials that conducted at normal velocities for at least 12 h postinfarction. The transmural extent of the infarct was verified with tetrazolium blue staining at the end of the experiment. In the other four dogs, compound action potentials were generated in cardiopulmonary nerves as described above and then ventricular fibrillation was produced to assess the effects of global anoxia on the function of axons coursing in cardiac nerves. Following the onset of ventricular fibrillation, compound action potentials were generated in these nerves in C fibers for up to 2 h, in B fibers for up to 4 h, and in A fibers for at least 12 h. However, the conduction velocities of these axons was gradually reduced over these periods of time, indicating that, in contrast to the function of axons coursing over a transmural myocardial infarction, their function gradually deteriorated. Thus, by directly assessing the function of axons coursing over a transmural infarction, it is concluded that an acute transmural myocardial infarction does not significantly modify the function of intrinsic cardiac nerves coursing over such an infarct.
Renal and hepatic glutathione pool modifications in response to depletion treatments
Authors: Rodríguez Joaquín V. , Torres Adriana M. , Elías María M.
Published: April 2011

In this study we examined the response of the renal and hepatic glutathione (GSH) pool in rats to drastic GSH depletion treatments. For this purpose, we used a protein-free diet, starvation, and the injection of varying doses of diethyl maleate as depleting agents. We analysed GSH levels in both kidney and liver tissue homogenates after rats were fed a protein-free diet for 2 or 7 days or starved for 1, 2, or 3 days, as well as after diethyl maleate administration in a single maximal dose or in varying doses. The results indicated that the liver GSH pool was always more labile than the kidney GSH pool. Moreover, kidney GSH levels were almost unchanged after 7 days on a protein-free diet or after 2 days of starvation, while liver showed significant changes in GSH levels. When we analysed the repletion rate, kidney had higher kinetic parameters (k = 0.148 h−1) than liver (0.097 h−1). We conclude that efficient mechanisms of maintaining GSH levels exist in the kidney and these may serve to avoid GSH diminution and hence preserve renal function during states of GSH depletion.
Diets alter jejunal morphology and brush border membrane composition in streptozotocin-diabetic rats
Authors: Keelan M. , Walker K. , Rajotte R. , Clandinin T. , Thomson A. B. R.
Published: April 2011

Previous studies have demonstrated enhanced active and passive uptake of many nutrients in animals with experimental diabetes. These changes in absorption cannot be explained by differences in intestinal morphology, although the brush border membrance (BBM) phospholipids do change in diabetes. Manipulation of diet produces alterations in intestinal uptake of lipids and glucose. This study was undertaken to determine the effect of diet and diabetes on jejunal morphology and BBM lipid composition. Rats were rendered hyperglycemic with streptozotocin and were fed for 2 weeks on a diet that was high or low in carbohydrate, essential fatty acids, cholesterol, or protein. In both control and diabetic rats, these diets produced changes in villus height and BBM sucrase and alkaline phosphatase activities. In both control and diabetic rats, BBM phospholipids were unaffected by changes in the dietary content of essential fatty acids, cholesterol, or protein, but total BBM phospholipid content was reduced in animals fed low as compared with high carbohydrate diet. Total BBM phospholipid content was higher in diabetic than in control animals fed the low protein diet, whereas BBM phospholipid content was lower in diabetic than in control animals fed the high carbohydrate diet, and was even lower in diabetic animals fed the low as compared with the high carbohydrate diet. These changes in total phospholipids were due to alterations in the BBM content of phospholipids containing choline. In control animals, BBM cholesterol was higher in rats fed the low as compared with the high cholesterol diet, or the low as compared with the high protein diet. In diabetic rats, BBM cholesterol was higher than in animals fed the low as compared with the high essential fatty acid or high protein diet. BBM cholesterol was higher in diabetic than in control rats only when fed the low essential fatty acid diet. The results show that (i) diabetes and dietary manipulation produce changes in villus morphology, BBM enzymes, and lipids, but there is no apparent relationship between alterations in the various parameters measured; and (ii) diet and diabetes may alter lipid uptake as a result of qualitative and quantitative changes in the choline phospholipids in the intestinal brush border membrane.
Acetylcholine reduces inward rectification on thymus-derived macrophage cells in culture
Authors: Moody-Corbett F. , Brehm P.
Published: April 2011

Cultures prepared from dissociated rat thymus were examined 1–2 weeks after plating. Macrophage cells were identified by their adherence, morphological appearance, and ability to phagocytize carbon particles or heat-inactivated Staphylococcus aureus. Whole cell current recordings from macrophage cells revealed an inward current at potentials more negative than the equilibrium potential for potassium and an outward current at potentials more positive than −40 mV in normal recording solution. Acetylcholine or muscarine caused a reduction in inward current but did not alter the outward current. The inward current and acetylcholine effect were seen at less negative potentials by decreasing the potassium equilibrium potential and both were blocked by the addition of cesium to the external recording solution. These results indicated that the inward current was mediated by potassium through the inward or anomalous rectifier. Physiologically, the action of acetylcholine on the inward rectifier of these macrophage cells may be mediated by cholinergic innervation of the thymus.
Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma
Authors: Erlichman Charles , Rauth A. Michael , Battistella Rena , Fine Sheldon
Published: April 2011

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t½λ1 of 9.8 ± 1.2 (SEM) min and mean t½λz of 64.1 ± 8.9 (SEM) min. The large variation observed in t½λz was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t½λz or the area under the curve. This may be due to (i) a failure to monitor active metabolites of mitomycin C; (ii) other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or (iii) the small number of courses associated with thrombocytopenia (<100 000/mm3). Our study indicates that (i) an interaction of drug dose and treatment course may be associated with increasing t½λz; (ii) the renal clearance contributes a small component of mitomycin C elimination; (iii) metabolites of mitomycin C cannot be detected by the present HPLC technique; and (iv) routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.
Spinal actions of substance P analogues on cardiovascular responses in the rat: a structure–activity analysis
Authors: Couture Réjean , Gupta Alka , Kérouac René , Escher Emanuel , Regoli Domenico
Published: April 2011

Ten substance P (SP) analogues were tested for their effects on mean arterial pressure and heart rate following intrathecal administration in the pentobarbital anaesthetized rat. The 10 analogues are [D-Pro4,D-αNpa7,9,10]SP(4–11) (A-I),(D-αNpa7,9,10]Sp (A-II);[D-Trp7,9,10]SP (A-III),[D-Pro4,D-Npa7,9, Phe11]SP(4–11) (A-IV),D-Pro4, D-βNpa7,D-αNpa9,D-Phe11]SP(4–11) (A-V), [D-Pro4,Lys6,D-Trp7,9,10, Phe11]SP(4–11) (A-VII),[D-Pro4,D-Trp7,9,10,Phe11]SP(4–11) (A-X),[D-Pro4,D-Trp7,9,10, Trp11]SP(4–11) (A-VIII),[D-Trp7,9,10, Trp11]SP (A-IX), and [D-Pro4,D-Phe7,9,10, Phe11]SP(4–11) (A-X). At 6.5 nmol, the analogues containing the amino acid D-Npa (A-I, A-II, A-IV, and A-V) or D-Phe (A-X) in positions 7, 9, or 10 or SP or its C-terminal octapeptide are devoid of the long-lasting cardio- and vaso-depressor effects, which are otherwise seen with analogues containing the amino acid D-Trp (A-III, A-VI, A-VII, A-VIII, and A-IX) in the same positions. Some of the analogues containing D-Npa maintain the initial hypotensive effect seen with SP while the analogue containing D-Phe produces only a small hypertensive response. The 10 analogues when tested at a dose that failed to alter basal mean arterial pressure and heart rate did not block the cardiovascular responses elicited by SP and no cross desensitization was observed between SP and these analogues. It appears that these SP analogues exert cardiovascular effects in the rat spinal cord probably without interacting with SP receptors.
Chemoprevention of Mutation and Cancer La chimioprévention de la mutation et du cancer
Authors: Goldberg Mark T.
Published: April 2011

The mortality rate from all types of cancers rose by about 0.5% per annum from 1980 to 1984 in both males and females in Canada (National Cancer Institute of Canada 1986). This suggests that although advances in cancer diagnosis and therapy have improved the short-term prognosis and quality of life for many cancer patients, there has been little or no effect on the mortality rate for most common cancers. Increasingly cancer researchers are coming to the realization that prevention is the approach that is most likely to make an impact on cancer mortality rates. Attention has been drawn particularly to the potentially preventative influence of diet on the process of carcinogenesis (National Academy of Sciences 1982; Ames 1983). Although trends in the relationship between diet and cancer prevention have been recognized (Phillips 1980; Hirayama 1979), it has been difficult to identify the specific chemical or molecular components of our diet to which anticarcinogenic properties are attributable. The use of short-term in vivo and in vitro assays has greatly facilitated this research; one no longer need wait 12 to 18 months for tumours to appear. As a result, we have a primitive but rapidly expanding understanding of the mechanisms of chemoprevention of cancer.This symposium was organized to examine some of the recent advances in chemoprevention research. The focus has been placed on common dietary components and on methods that yield quick but biologically relevant results.The symposium was jointly sponsored by the Society of Toxicology of Canada and the Pharmacological Society of Canada, whose support is gratefully acknowledged.
Central and peripheral actions of salicylate in altering nonpyrogenic thermoregulation of rats
Authors: McCain Hulon W. , Mundy Roy L.
Published: April 2011

The effects on body temperature of intracerebroventricular and intraperitoneal sodium salicylate were evaluated in anesthetized and nonanesthetized, nonrestrained rats. Also, the effects of various neurotransmitter receptor blocking drugs were evaluated on salicylate-induced hypothermia of nonanesthetized animals. Sodium salicylate, 150–350 mg/kg induced a dose-related hypothermia of unanesthetized animals. However, in anesthetized animals, marked hyperthermia was observed. In unanesthetized, unrestrained rats, intracerebroventricular administration of 1.0 mg/h salicylate caused greater hypothermia than peripheral administration of salicylate, 350 mg/kg. Salicylate hypothermia was unaffected by para-chlorophenylalanine, cyproheptadine, or naloxone, and was only partially inhibited by pimozide. These results strongly suggest a potent direct action of salicylate within the central nervous system to induce hypothermia, and suggest possible involvement of dopaminergic neurons in this process.
Simultaneous measurements of Ca2+ currents and intracellular Ca2+ concentrations in single skeletal muscle fibers of the frog
Authors: Brum G. , Stefani E. , Rios E.
Published: April 2011

The relationship between Ca2+ current amplitudes and myoplasmic Ca2+ transients was studied in single muscle fibers. Segments of muscle fibers were voltage-clamped in a double Vaseline gap chamber. Ca2+ transients were measured as an optical signal derived from the interaction between Ca2+ and the dye antipyrylazo III. The cells were maintained at −90 mV. Ca2+ currents were detected at pulse potentials to −50 mV, reached a maximum value at 0 mV, were reduced in size for larger depolarizations, and reversed at about 40 mV. Ca2+ transients were also detected at −50 Mv and progressively increased in size with larger pulse potentials up to 10 mV. Depolarizations to voltages greater than 10 mV did not further increase the size of the transient. The magnitude and time course of transients from 10 to 70 mV were almost identical. Ca2+ fluxes into the myoplasm (Ca2+ input fluxes) were calculated from the Ca2+ transients applying a removal model. The size of the input fluxes increased with depolarization up to 0 mV. Between 0 and 70 mV the peak input flux slightly increased, while the flux measured at 200 ms remained unchanged. In conclusion, Ca2+ transients and input fluxes were not reduced during pulses to large positive potentials, even though a drastic reduction of Ca2+ current occurred at these potentials. These observations make it very unlikely that a voltage-dependent Ca2+ entry is the triggering signal for contraction.
Measurements of intracellular free Ca2+ in mammalian central neurons
Authors: Krnjević K. , Morris M. E. , MacDonald J. F. , Ropert N.
Published: April 2011

Neutral carrier-containing Ca2+-selective microelectrodes were used to record the cytoplasmic free Ca2+ concentration ([Ca2+]i) in spinal cells in cats and in hippocampal cells of rats (in situ). The mean [Ca2+]i in motoneurons was close to 1 μM. Antidromic or direct stimulation for 30 s at 10 Hz increased [Ca2+]i by a mean of 90 nM. Such a small increase in [Ca2+]i and its slow decay (with a mean half-time of 23 (SD ± 14.5) s) indicate very effective intracellular sequestration of Ca2+. Orthodromic stimulation consistently evoked smaller increases in [Ca2+]i. A much larger rise of interneuronal [Ca2+]i was evoked by stimulation of dorsal roots: by contrast intra-axonal recording (in motor or sensory fibres) failed to reveal any increase in [Ca2+]i in response to stimulation at 100 Hz. In the hippocampus, presumably because of poorer recordingconditions, resting values of [Ca2+]i were higher (mean 8.5 μM). Repetitive stimulation of the fimbria–commissure at 5–20 Hz for 30 Hz, had variable effects on [Ca2+]i. Very large increases (to > 200 μM) were elicited repeatedly in some cells, either near the end of the tetanic stimulation or after a 20–30 s delay. Such major increases, which were associated with population cell discharges in bursts, may be related to long-term changes in hippocampal neuronal properties that are evoked by tetanic stimulation. Both in the spinal cord and the hippocampus, probable intraglial recordings showed relatively high mean levels of [Ca2+]i (about 30 μM).
Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus
Authors: Norman Laurie J. , Challis John R. G.
Published: April 2011

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113–116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126–130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma Cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or Cortisol response to oCRF, AVP, or oCRF + AVP at d 136–140, but dexamethasone suppressed basal ACTH and Cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113–116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and Cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly. Our results suggest different controls of basal and stimulated ACTH release from the pituitary at d 113–116 of gestation. Our findings would be consistent with the pituitary as a level of action for the negative feedback effect of corticosteroids on stimulated ACTH release throughout the last third of pregnancy in fetal sheep.
Histochemical fiber type distribution and epinephrine sensitivity in normal and cross-transplanted rat muscles
Authors: Kennedy John M. , Mong Franz S. F. , Poland James L.
Published: April 2011

The metabolic integrity of fully regenerated transplants was investigated by measuring induced changes in glycogen concentration. The extensor digitorum longus and the soleus muscles were cross transplanted: the extensor digitorum longus into the soleus muscle bed (SOLT) and the soleus muscle into the extensor digitorum longus bed (EDLT). The histochemical fiber type distribution of the regenerated muscles was determined and was found to transform in cross-transplanted EDLT and SOLT. After transplantation and regeneration, both muscles had initially low glycogen concentrations. However, the EDLT glycogen concentration was not significantly different from that of the contralateral extensor digitoium longus control muscle after 60 days. In the SOLT, glycogen gradually increased but remained less than in the contralateral soleus control muscle. SOLT and control soleus muscles responded with a significant glycogen depletion to an epinephrine dose two orders of magnitude less than the lowest dose affecting glycogen levels in EDLT and extensor digitorum longus muscles. These results indicate that transplanted muscles are capable of regenerating normal glycogenolytic responses and that the sensitivity of the response observed depends on the site of transplantation and is related to the type of innervation and histochemical fiber type.
Influence of cold and warm acclimation on neuronal responses in the lower brain stem
Authors: Hinckel P. , Perschel W. T.
Published: April 2011

Neurons in two lower brain stem areas, the nucleus raphe magnus and the subcoeruleus region, have been shown to be part of the thermoafferent system. It is concluded from microcut experiments in unanaesthetized guinea pigs that inhibition of shivering caused by nucleus raphe magnus stimulation is mediated partly by ascending and partly by descending efferents of the nucleus raphe magnus. Electrical stimulation of the subcoeruleus area caused excitatory metabolic responses. Interruption of the ascending efferents of the subcoeruleus area did not prevent the metabolic activation. It is concluded that the excitatory responses are partly mediated by descending efferents of the subcoeruleus area. The descending pathways project mainly to motoneurone pools and to dorsal horn cells. In cold-acclimated guinea pigs, the average maximum activity of bell-shaped subcoeruleus cold-responsive units was reduced significantly in comparison with cold-responsive neurons in animals acclimated to normal room temperature. Furthermore, peak activity of warm-responsive units in the nucleus raphe magnus was larger in cold-acclimated animals than in animals acclimated to normal room termperature. These neuronal changes may contribute via descending lower loops and via ascending upper loops to long-term slope reduction of metabolic cold defence and shivering threshold displacements.
Sex- and species-related differences in the biotransformation of isosorbide dinitrate by various tissues of the rabbit and rat
Authors: Tam G. S. , Marks G. S. , Brien J. F. , Nakatsu K.
Published: April 2011

The biotransformation of isosorbide dinitrate (ISDN) by various tissues of the rabbit and rat was examined. Incubation of 2 × 10−7 M ISDN at 37 °C with tissue homogenates of liver, lung, kidney, intestine, skeletal muscle, aorta, and erythrocytes from the rabbit and rat resulted in a significant disappearance of ISDN after a 30-min incubation (also, 5-min incubation for liver). The disappearance of ISDN in each tissue homogenate was accompanied by an equimolar production of the mononitrate metabolites, isosorbide-2-mononitrate (2-ISMN) and isosorbide-5-mononitrate (5-ISMN), with the exception of liver homogenates where the loss of ISDN could not be accounted for by mononitrate formation. The relative rate of ISDN disappearance in various tissue homogenates was for the male rabbit, liver > lung ≈ intestine > kidney > erythrocytes ≈ skeletal muscle ≈ aorta; for the female rabbit, liver > kidney ≈ lung ≈ intestine > erythrocytes ≈ skeletal muscle ≈ aorta; and for the male rat, liver > intestine > erythrocytes > skeletal muscle > lung ≈ kidney. A sex difference in the percent disappearance of ISDN was observed in homogenates of lung and intestine from male and female rabbits. In addition, a sex difference in the ratio of metabolite (2-ISMN/5-ISMN) formed by denitration of ISDN was seen in homogenates of lung, skeletal muscle, and erythrocyte lysate. There was a species difference between the male rabbit and male rat, with respect to the loss of ISDN exhibited during incubation of ISDN with liver homogenates for 5 min; this was also observed for homogenates of lung, kidney, and intestine during a 30-min incubation. In addition, a similar species difference was observed for metabolite ratios obtained from these incubations. These results indicate that biotransformation of ISDN by liver and extrahepatic tissues may contribute to the high systemic clearance of this drug. The observed sex and species differences in the rate of ISDN disappearance and the metabolite ratio (2-ISMN/5-ISMN) in the various tissues may be due to hormonal and (or) genetic differences.
Confluence of barosensory and nonbarosensory inputs at neurons in the ventrolateral medulla in rabbits
Authors: Terui Naohito , Saeki Yuka , Kumada Mamoru
Published: April 2011

In urethane-anesthetized rabbits, 209 spontaneously active neurons that responded to stimulation of aortic nerve A fibers were found within the ventrolateral medulla (VLM). The neurons, termed barosensory VLM neurons, were inhibited, except for three instances, by stimulation of A fibers. Forty-seven percent of barosensory VLM neurons tested (74 of 159) were activated antidromically by electrical stimulation of the dorsolateral funiculus at the C2 level. Activity of barosensory VLM neurons was enhanced by stimulation of carotid body chemoreceptors or the posterior hypothalamic area, whereas it was diminished by increases in arterial pressure elicited by injection of phenylephrine. Barosensory VLM neurons responded variously to stimulation, with two to three pulses at 40 or 100 Hz, of spinal afferents of cutaneous and muscle origins and the spinal trigeminal complex. Although stimulation of one group of somatosensory fibers could evoke different patterns of neuronal responses consisting of excitatory and inhibitory components, the following responses were most often encountered. Group II cutaneous afferents caused an inhibition. Recruitment of group III afferents brought about a brief excitatory component preceding it. Activation of group IV cutaneous fibers added a long latency excitatory component. Excitation of groups III and IV muscle afferents most often resulted in an inhibition, whereas stimulation of the spinal trigeminal complex elicited various combinations of excitatory and inhibitory components. These results are consistent with the view that neurons in the ventrolateral medulla receive barosensory and nonbarosensory inputs from various peripheral and central sources and participate in the control of sympathetic vasomotor activity and arterial pressure.
Mechanisms for the release of atrial natriuretic peptide
Authors: Rankin A. J.
Published: April 2011

In assessing the role that atrial natriuretic peptide (ANP) might have in the homeostasis of fluid volume and blood pressure, it is important to define the physiological and pathophysiological conditions that determine its release into the circulation. There is substantial evidence that ANP is released through atrial distension under a variety of conditions. There are also some indications that ANP may be released through humoral factors, although it is not clear whether this is a result of direct action on the myocytes or simply a result of ensuing haemodynamic changes. There is no evidence to suggest that ANP can be released through stimulation of efferent fibres innervating the atria, but it may be released as a result of changes in myocardial work and oxygen consumption. Plasma levels of ANP are elevated in several disease states and that release appears to be a result of the haemodynamic disturbances in those conditions.
Enteric opioid neurons modulate the basal tone of the isolated puppy ileum
Authors: Neya T. , Mizutani M. , Nakayama S.
Published: April 2011

We studied the role of enteric opioid neurons in the spontaneous motility of the longitudinal muscle in the isolated puppy ileum. Regular fluctuations in tone that rose above and returned to the basal level occurred at an interval of 4.7 ± 0.3 min. Naloxone (10−8 and 10−7 M) reduced the spontaneous tonic contraction by 42.6 ± 11.6% (p < 0.02) and 77.0 ± 3.6% (p < 0.001), respectively. Tetrodotoxin (3.1 × 10−7 M) and atropine (10−7 M) terminated the fluctuations. Met- and Leu-enkephalins (10−9–10−8 M) caused tonic contraction which was abolished by tetrodotoxin and atropine. The contractile response produced by transmural electrical stimulation was reduced by naloxone (10−7 M). This response was also abolished by atropine and tetrodotoxin. These results suggest that enteric opioid neurons are spontaneously active and might operate, at least in part, to raise the basal tone of the longitudinal muscle in the puppy ileum through a cholinergic excitatory mechanism.
Transhepatic absorption and biliary excretion of insulin
Authors: Zingg Walter , Rappaport Aron M. , Leibel Bernard S.
Published: April 2011

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.
Effect of catecholamines on porcine Sertoli and Leydig cells in primary culture
Authors: Renier G. , Gaulin J. , Gibb W. , Collu R. , Ducharme J. R.
Published: April 2011

The accumulation by purified immature porcine Leydig and Sertoli cells of cyclic adenosine 3′,5′-monophosphate in the presence of 1-methyl-3-isobuthylxathine was studied and their respective testosterone and 17β-estradiol production in response to catecholamines was assessed in vitro. These substances increased both basal and FSH-stimulated cyclic adenosine 3′,5′-monophosphate accumulation in Sertoli cells. In contrast, catecholamines slightly enhanced basal cyclic adenosine 3′,5′-monophosphate production but inhibited its human chorionic gonadotropin-stimulated accumulation by Leydig cells. Catecholamines had no effect on basal and stimulated testosterone release by these cells, while dopamine inhibited 17β-estradiol synthesis by Sertoli cells. Using various α- and β-adrenergic agonists and antagonists, β-receptors, likely of the β1-subtype, were shown to be present in both cell lines. Taken together these data suggest the presence of a cyclic adenosine 3′,5′-monophosphate-linked adrenergic receptor in porcine Leydig and Sertoli cells, the role of which remains to be determined.
Effect of exercise on net hepatic uptake of lactate, pyruvate, alanine, and glycerol in sheep
Authors: Brockman Ronald P.
Published: April 2011

Gluconeogenesis increases during exercise, which is associated with elevated concentrations of lactate and glycerol in blood. This study was undertaken to determine if the exercise-induced increase in gluconeogenesis is due to increased hepatic extraction efficiency of glucose precursors. The net hepatic uptake and extraction ratios were determined for selected glucose precursors before and during exercise. The hepatic uptake of lactate and glycerol increased during exercise in fed and fasted animals, but extraction ratios of lactate and glycerol increased only in fed animals. Thus, the exercise-induced increase in gluconeogenesis is due to increased substrate supply and to hepatic extraction efficiency under certain circumstances, which is comparable to the situation in man.
Endometrial prostaglandins and menorrhagia: influence of a prostaglandin synthetase inhibitor in vivo
Authors: Tsang B. K. , Domingo M. T. , Spence J. E. H. , Garner P. R. , Dudley D. K. , Oxorn H.
Published: April 2011

Prostaglandin levels in the human endometrium were determined on day 2 of the menstrual cycle in eumenorrheic subjects and in patients with menorrhagia, dysmenorrhea, or both. Menorrhagic subjects had significantly higher levels of endometrial prostaglandins of the E and F series when compared with eumenorrheics. Prostaglandin E levels were markedly higher than prostaglandin F. In 10 menorrhagic subjects who completed a double-blind clinical study on the effectiveness of mefenamic acid in lowering menstrual blood loss, 9 exhibited statistically significant reduction in endometrial prostaglandin levels. A decrease in menstrual blood loss was also noted during mefenamic acid treatment in these patients. These findings are consistent with the concept that abnormally high uterine prostaglandin levels may be an important etiologic factor in menorrhagia and support the notion that one of the mechanisms of action of nonsteroidal anti-inflammatory agents in the treatment of this menstrual disorder is inhibition of endometrial prostaglandin production.
Characteristics of beta-adrenoceptors in tracheal smooth muscle of guinea pig sensitized by egg albumin
Authors: Nakagoshi Akihiro , Koike Katsuo , Takayanagi Issei
Published: April 2011

The effect of pretreatment with egg albumin was examined on the beta-adrenoceptors in guinea pig isolated trachea. Befunolol and carteolol acted as partial agonists and their pA2 values were significantly larger than their corresponding pD2 values in tracheae from both untreated guinea pigs and those treated with egg albumin, suggesting that the beta-adrenoceptors contain two different affinity sites. The Scatchard plot of specific [3H]befunolol binding showed two affinity sites of the receptor (high and low affinity sites) in tracheae from both untreated animals and those treated with egg albumin. The pKD values of befunolol for both low and high affinity sites were in agreement with their respective pD2 and pA2 values. The intrinsic activities of befunolol and carteolol and the pD2 values of the test drugs were decreased by the treatment with egg albumin. The treatment with egg albumin also decreased the total amount of the two affinity sites of the receptor without any change in affinity. The present results support the partial blockade of beta-adrenoceptors in asthma proposed by Szentivanyi.
Spinal action of neurokinins in the rat: effects on mean arterial pressure, heart rate, and vascular permeability
Authors: Hasséssian Harout , Couture Réjean , Jacques Line
Published: April 2011

In urethane-anaesthetized rats, the intrathecal administration of 6.5 nmol of substance P (SP), neurokinin A (NKA), or neurokinin B (NKB) at the T8–T10 level of the spinal cord enhances mean arterial pressure and heart rate. However, in the pentobarbital-anaesthetized rat, while NKB produces no effect on mean arterial pressure, NKA produces a biphasic change and SP, a depressor response. All three neurokinins elicit a tachycardia. The following rank order of potency SP ≥ NKA > NKB is observed in relation to these cardiovascular responses when either one of the two anaesthetics is used. The low cardiovascular activity of NKB cannot be attributed to its hydrophobicity, as the water soluble analogue of NKB, [Arg0] NKB, elicits a response as weak as the native peptide. In pentobarbital-anaesthetized rats, the intrathecal administration of 6.5 nmol of SP, also enhances plasma protein extravasation in cutaneous tissues of the back, the hind paws, and the ears. In this response NKA and NKB are either inactive (skin of hind paws) or less potent than SP (ears and dorsal skin). These findings agree with the hypothesis that in the rat spinal cord, the neurokinin receptor producing changes in mean arterial pressure, heart rate, and vascular permeability is of the NK-1 subtype.
Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect
Authors: Krayacich J. , Kline R. L. , Mercer P. F.
Published: April 2011

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 μg/min, i.v.), an α1 adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (−67 ± 9 vs. −33 ± 8%), glomerular filtration rate (−60 ± 9 vs. −7 ± 20%), urine flow (−61 ± 7 vs. −24 ± 11%), sodium excretion (−51 ± 15 vs. −32 ± 21%), and fractional excretion of sodium (−50 ± 9 vs. −25 ± 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (−54 ± 10 vs. −30 ± 14%), glomerular filtration rate (−51 ± 11 vs. −19 ± 17%), urine flow (−55 ± 10 vs. −39 ± 10%), sodium excretion (−70 ± 9 vs. −59 ± 11%), and fractional excretion of sodium (−53 ± 10 vs. −41 ± 10%). These results suggest that vascular and tubular supersensitivity to norepinephrine in chronically denervated kidneys is due to postsynaptic changes involving α1-adrenergic receptors.
Effects of yohimbine and desipramine on cardiac noradrenaline release and ventricular arrhythmias during acute coronary artery occlusion and reperfusion in anesthetized dogs
Authors: Yamaguchi Nobuharu , Lamontagne Daniel , Boudreau Ghislain , Nadeau Reginald , Champlain Jacques de
Published: April 2011

Effects of yohimbine (YHMB, an α2-antagonist) and desipramine (DMI, a neuronal uptake inhibitor) were compared on cardiac noradrenaline (NA) release either upon left ansa subclavia nerve stimulation during acute occlusion of the left anterior descending coronary artery (LAD) or upon subsequent LAD reperfusion without stimulation in anesthetized dogs. In control dogs, before LAD occlusion, coronary sinus (CS) NA output increased from 5.4 ± 1.0 to 26.8 ± 4.0 ng/min (p < 0.05) upon stimulation (2 Hz, 30 s). The response to stimulation remained unchanged 25 min after LAD occlusion. During reperfusion 60 min after occlusion, the output of CS-NA and lactate increased from 6.1 ± 0.8 to 51.3 ± 19.4 ng/min (p < 0.05) and from 2.7 ± 0.5 to 6.7 ± 1.3 mg/min (p < 0.05), respectively. In dogs treated with YHMB, the stimulation-induced increase in NA output was potentiated at least fourfold (p < 0.05) either before or during LAD occlusion, but not during reperfusion. In dogs receiving DMI, stimulation-induced CS-NA output was enhanced to a similar extent (approximately twofold, p < 0.05) either before or during occlusion, while reperfusion-induced NA output was markedly potentiated by approximately ninefold (p < 0.05). Maximum dP/dt of left ventricular pressure remained unchanged upon reperfusion in all groups. The total arrhythmic ratio in the drug-treated groups did not significantly differ from the ratio in control dogs upon either stimulation or reperfusion. The data suggest that an abrupt increase in NA output upon reperfusion may result from a washout of NA locally accumulated in the ischemic and (or) peri-ischemic region during the preceding occlusion period, and that N A thus released does not have substantial hemodynamic effects. The results indicate that in the presence of YHMB or DMI, the potentiated increase in NA release in response to either nerve stimulation during LAD occlusion or to reperfusion without stimulation did not aggravate ventricular arrhythmia, most probably owing to the antiarrhythmic properties of these substances.
Mechanisms of excitatory actions of neurotensin on canine small intestinal circular muscle in vivo and in vitro
Authors: Fox J. E. T. , Kostolanska F. , Daniel E. E. , Allescher H.-D. , Hanke T.
Published: April 2011

We have shown previously that close intra-arterial injections of neurotensin in vivo inhibited phasic activity induced by field stimulation of the canine small intestine during anaesthesia but had little effect during quiescence. In contrast, in vitro in the present study, full thickness strips of the muscularis externa cut in the circular axis responded to the lowest effective neurotensin concentrations (10−12 to 10−9 M) with an increase in frequency and amplitude of spontaneous contractions; as the concentration was increased from 10−8 to 10−7 M, neurotensin inhibited spontaneous activity. A small tonic contraction also occurred; it was maximal at 10−7 M. Since sufficient tetrodotoxin to block field-stimulated nerve responses did not significantly reduce any of these responses in vitro, the neurotensin responses in vitro did not appear to involve actions on nerves. Indomethacin did not alter the excitatory response to 10−11 M neurotensin but 5,8,11,14-eicosatetraynoic acid inhibited the excitatory response in a reversible fashion, without altering the response to acetylcholine. Thus excitation in vitro may require the release of excitatory metabolites of arachidonic acid via the lipoxygenase pathway. The neurotensin response in vivo was further studied by evaluating its actions against repetitive submaximal contractions induced by intra-arterial injections of acetylcholine given every minute. Doses that produced a short inhibition of the field-stimulated activity (10−11 to 10−10 mol intra-arterially) did not produce inhibition but 10−10 mol significantly increased the response to acetylcholine. Higher doses (10−9 mol) produced a significant inhibition of the first subsequent acetylcholine dose but no enhancement of later doses. Thus an excitatory response to neurotensin could be demonstrated in vivo only at lower doses. Our findings emphasize the difference in the responses to neuropeptides in vivo and in vitro and show that variations in arachidonate metabolism may contribute to these differences in vitro.
Migrating action potential complexes—a feature of normal jejunal myoelectric activity in the rat
Authors: Diamant S. C. , Scott R. B.
Published: April 2011

To determine if migrating action potential complexes (MAPCs) are a feature of normal intestinal motility, Hooded-Lister rats (100–150 g) were surgically prepared with three pairs of bipolar jejunal electrodes spaced 2.5 cm apart and with a jejunostomy tube for motility recording. Animals were studied conscious and unrestrained on postoperative day 14 after an 18-h fast. Intestinal myoelectric and motor activity was recorded for a 1-h interval in 24 animals that continued to fast and in 12 animals that were allowed to feed for 10 min. Fasting rats had a jejunal slow wave frequency of 32 ± 2 contractions/min which did not differ significantly after feeding. Migrating myoelectric complexes (MMC) were clearly identified in all fasting animals and had a cycle period of 10.0 ± 3.6 min. MAPCs were seen during phase II in 83% of MMCs and had an average distribution of 4.2 ± 3.9/MMC. Feeding abolished the MMC and initiated a continuous irregular pattern of electrical spiking and associated contractile activity. Migrating action potential complexes were seen after feeding with a frequency of 1.8 ± 0.4/min. It is concluded that MAPCs are a common feature of normal interdigestive phase II and also of postprandial jejunal motility in the rat. This supports the hypothesis that the MAPC is a basic propulsive motor pattern intrinsic to normal intestinal function.
The kinetics of drug–membrane interactions in human erythrocytes
Authors: Eskelinen Sinikka
Published: April 2011

The time course of the shape transformations and vesicle release in human erythrocytes caused by lysophosphatidylcholine and chlorpromazine was monitored using a light microscope – video recording technique. The time required for the erythrocytes to reach a stage I echinocytic shape decreased from 4.0 to 2.0 s, when the concentration of the lysophosphatidylcholine solution injected was increased from 1 to 25 μM. The time required to reach stage II decreased from 8.3 to 3.5 s and that required for vesicle release and the formation of stage IV spherocytes decreased from 78.0 to 11.6 s. Correspondingly, the time needed for the formation of stage I stomatocytes decreased from 2.3 to 1.0 s and that for stage II stomatocytes from 3.1 to 2.0 s, when the ambient chlorpromazine concentration was increased from 50 to 200 μM. The kinetics of the shape transformations of the erythrocytes were dependent on the ambient drug concentration. The rate of shape transformations could be predicted from a formula derived for the kinetics of the incorporation of the detergent into the cell membrane, providing that the affinity coefficient and mass transfer coefficient for drugs changed as a function of the free drug concentration. The results give a time scale for the drug–membrane interactions, i.e., the formation of stages I and II for drug–lipid bilayer interactions and the release of vesicles for drug–cytoskeleton interactions.
The action of quinolinate in the rat spinal cord in vitro
Authors: Magnuson D. S. K. , Peet M. J. , Curry K. , McLennan H.
Published: April 2011

The responses of dorsal horn neurones to the excitatory amino acids quisqualate, kainate, N-methyl-D-aspartate (NMDA), and quinolinate have been examined in an in vitro preparation of the rat spinal cord. The antagonism of these responses by iontophoretically applied D-(−)-2-amino-5-phosphonovalerate (DAPV), kynurenate, and acridinate was tested, and the results were compared with data obtained from the spinal cord in vivo. The pattern of antagonism was similar in both preparations, although the potencies of agonists and antagonists were found to be significantly greater in vitro. The antagonism of amino acid induced firing of neurones was also recorded during the application of DAPV and kynurenate in the bathing medium. Dose–response curves and IC50 values were determined for these antagonists against all four agonists. The responses to quinolinate were antagonized differently from those to NMDA, quisqualate, or kainate, suggesting that quinolinate does not act specifically through the NMDA receptor as it does in other regions, nor does it appear to act via two or more of the three archetypal amino acid receptors. These findings suggest that a fourth amino acid receptor responsible for quinolinate's action in the spinal cord may exist.
Impairment of gonadotropin binding occurs during membrane rigidification in plasma membrane samples prepared from regressed rat corpora lutea
Authors: Riley John C. M. , Carlson John C.
Published: April 2011

The effect upon human chorionic gonadotropin (hCG) binding of a 90-min incubation of plasma membranes prepared from the corpora lutea of control and prostaglandin F2α injected rats was studied. After incubation for 90 min with 1 mM CaCl2 at 40 °C, single point hCG binding assays at room temperature revealed a significant decrease in the degree of binding of approximately 50% in membrane samples prepared from regressed corpora lutea. The binding decrease in regressed samples did not occur if the incubation temperature was reduced to 35 °C or if calcium ion was replaced with magnesium. Scatchard analyses indicated that the decrease in binding capacity was the result of a loss of gonadotropin receptors rather than an affinity shift. Specific activities of two membrane-bound enzymes (Na+–K+ ATPase, 5′-nucleotidase) did not change in a correlative fashion during the incubation. In previous studies the same in vitro conditions caused a substantial and significant decrease in membrane fluidity, as determined by fluorescence polarization. Thus it appears that the membrane rigidification is of a specific nature and interferes with gonadotropin binding during luteolysis.