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PubMed1980

Carbon dioxide balance in rat stomach and peripheral tissue: effects of histamine.

Total carbon dioxide content of arterial, gastric venous, and peripheral venous blood of the rat has been measured by a gas extraction-gas solid chromatographic technique. In control animals total contents were 24 to 29 mmol/l and the venous/arterial ratio 1.148 +/- 0.020 (xav +/- SEM). Net change of carbon dioxide content (delta CO2) was 1.17 +/- 0.56 and 1.11 +/- 0.45 mmol/l in gastric and peripheral circulations and these were not significantly different from each other or zero. Infusion of histamine at 10 mg/kg/h led to oscillations in delta CO2 with peaks as high as 4.7 mmol/l and a period of 20 min. Similar oscillations occurred in the venous/arterial ratio with values up to 1.35. The results confirm previous reports of oscillations of carbon dioxide venous/arterial ratios induced by histamine as revealed by pulse radiolabeling experiments. The positive, if oscillatory, carbon dioxide balance in the presence of histamine supports the concept of sequestration of carbon dioxide in tissue with subsequent release on histamine stimulation.

Acid-Base Equilibrium↗
PubMedDate not supplied

Glutamate receptors in peripheral tissues: current knowledge, future research, and implications for toxicology.

We illustrate the specific cellular distribution of different subtypes of glutamate receptors (GluRs) in peripheral neural and non-neural tissues. Some of the noteworthy locations are the heart, kidney, lungs, ovary, testis and endocrine cells. In these tissues the GluRs may be important in mediating cardiorespiratory, endocrine and reproductive functions which include hormone regulation, heart rhythm, blood pressure, circulation and reproduction. Since excitotoxicity of excitatory amino acids (EAAs) in the CNS is intimately associated with the GluRs, the toxic effects may be more generalized than initially assumed. Currently there is not enough evidence to suggest the reassessment of the regulated safety levels for these products in food since little is known on how these receptors work in each of these organs. More research is required to assess the extent that these receptors participate in normal functions and/or in the development of diseases and how they mediate the toxic effects of EAAs. Non-neural GluRs may be involved in normal cellular functions such as excitability and cell to cell communication. This is supported by the wide distribution in plants and animals from invertebrates to primates. The important tasks for the future will be to clarify the multiple biological roles of the GluRs in neural and non-neural tissues and identify the conditions under in which these are up- or down-regulated. Then this could provide new therapeutic strategies to target GluRs outside the CNS.

Animals↗
PubMed1993

Localization of neurotrophin-3-like immunoreactivity in peripheral tissues of the rat.

Neurotrophin-3 (NT-3) mRNA is widely distributed in both the peripheral and central nervous systems but neither the distribution of the native factor nor its physiological function is known. In the present study we produced and characterized an antibody to a synthetic peptide and showed that it specifically recognised endogenous rat and recombinant human NT-3 (rNT-3), but not mouse nerve growth factor and recombinant brain derived-neurotrophic factor. NT-3-like immunoreactivity (NT-3-ir) was detected within the distal tubular cells of the kidney, the zona glomerulosa and reticularis of the adrenal cortex, ganglion cells of the adrenal medulla, red pulp of the spleen, epithelial cells of the intestinal villi and parenchymal cells of the liver. Within peripheral ganglia, NT-3-ir was observed in a subpopulation of large sensory neurons of dorsal root, trigeminal and cochleovestibular ganglia but not in principle neurons of the sympathetic ganglia. These results provide the first evidence for the localization of NT-3-ir and indicate its presence in various peripheral organs and large sensory neurons. We conclude that NT-3 may function outside the nervous system in addition to a neurotrophic role within large sensory neurons.

Animals↗
PubMed2005

Interleukin-6 levels fluctuate with the light-dark cycle in the brain and peripheral tissues in rats.

Interleukin-6 (IL-6) has been implicated in excessive daytime sleepiness (EDS) in humans, and exogenous IL-6 also induces sleep alterations both in humans and rats. The IL-6 levels in human blood vary with the light-dark cycle with IL-6 levels being high during the dark period and low during the light period, whereas in the pituitary of rats the IL-6 levels are elevated during the light period compared to the dark period. However, it is unknown whether IL-6 in the brain is affected by the light-dark cycle. We hypothesized that IL-6 levels in the brain are regulated by the light-dark cycles and are elevated during the period that is predominantly occupied by sleep. To test this hypothesis, we measured IL-6 levels in the brain, blood, and adipose tissue of rats across light-dark cycle every 4 h. IL-6 levels were significantly higher during the light period than during the dark period in the cortex, hippocampus and hypothalamus. In the brainstem, IL-6 levels did not significantly vary across the light-dark cycles. IL-6 levels in the blood and adipose tissues were also significantly higher during the light period than during the dark period. IL-6 levels were positively correlated between the blood and adipose tissue, between hypothalamus and blood, and between the hypothalamus and hippocampus. These observations suggest that IL-6 levels vary across the light-dark cycle among different tissues and that IL-6 levels are elevated both centrally and peripherally during the period predominantly occupied by sleep but decreased during the period that primarily consists of wakefulness.

Adipose Tissue↗
PubMed1986

In vivo insulin resistance in individual peripheral tissues of the high fat fed rat: assessment by euglycaemic clamp plus deoxyglucose administration.

We have examined peripheral insulin action in conscious rats chronically fed high fat (60% calories as fat) or high carbohydrate (lab chow) diets using the euglycaemic clamp plus 3H-2-deoxyglucose technique. A response parameter of individual tissue glucose metabolic rate (the glucose metabolic index, based on tissue deoxyglucose phosphorylation) was used to assess diet effects in eight skeletal muscle types, heart, lung and white and brown adipose tissue. Comparing high fat with high carbohydrate fed rats, basal glucose metabolism was only mildly reduced in skeletal muscle (only diaphragm was significant, p less than 0.05), but was more substantially reduced in other tissues (e.g. white adipose tissue 61% and heart 33%). No evidence of basal hyperinsulinaemia was found. In contrast, widespread insulin resistance was found during the hyperinsulinaemic clamp (150 mU/l) in high fat fed animals; mean whole body net glucose utilization was 34% lower (p less than 0.01), and the glucose metabolic index was lower in skeletal muscle (14 to 56%, p less than 0.05 in 6 out of 8 muscles), white adipose (27%, p less than 0.05) and brown adipose tissue (76%, p less than 0.01). The glucose metabolic index was also lower at maximal insulin levels in muscle and fat, suggesting the major effect of a high fat diet was a loss of insulin responsiveness. White adipose tissue differed from muscle in that incremental responses (maximal insulin minus basal) were not reduced by high fat feeding. The heart showed an effect opposite to other tissues, with an increase in insulin-stimulated glucose metabolism in high fat versus chow fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1990

Distribution and characterization of diazepam binding inhibitor (DBI) in peripheral tissues of rat.

We studied the expression and distribution of the polypeptide diazepam binding inhibitor (DBI) in rat peripheral organs by immunocytochemistry, radioimmunoassay, Northern blot analysis and binding assay. Variable amounts of the DBI peptide and DBI mRNA were found in all the tissues examined (liver, duodenum, testis, kidney, adrenal gland, heart, ovary, lung, skeletal muscle and spleen), with the highest level of expression in liver (220 pmol of DBI/mg protein) and the lowest in spleen (11 pmol of DBI/mg protein). A good correlation between DBI-like immunoreactivity (DBI-LI) and mRNA content was found in all tissues except the heart. The immunohistochemical analysis revealed discrete localization of DBI-LI in cell types with specialized functions: for example, the highest DBI-LI content was found in steroid-producing cells (glomerulosa and fasciculata cells of adrenal cortex, Leydig cells of testis); lower DBI-LI immunostaining was found in epithelial cells specialized for water and electrolyte transport (intestinal mucosa, distal convoluted tubules of kidney). Hepatic cells contained moderate immunoreactivity however the total content of DBI in liver is relatively high and is due to the diffuse presence of DBI in every hepatocyte. Cells with high expression of DBI have been shown to contain a high density of mitochondrial benzodiazepine (BZ) binding sites. This observation led us to perform a competitive binding assay between DBI and [3H]PK11195 (a ligand for the mitochondrial BZ binding sites) on mitochondrial membranes of adrenal cortical cells. In this experiment, DBI yielded an apparent competitive inhibition of the binding of PK11195 to the BZ binding sites. Our data support a possible role for DBI as endogenous regulator of intracellular metabolic functions, such as steroidogenesis, via the mitochondrial BZ receptors.

Animals↗
PubMed1988

Influence of substrate background on peripheral tissue responses to growth hormone.

To evaluate the effects of substrate and hormonal background on the peripheral response to methionyl human growth hormone (met-hGH), metabolic measurements were performed in 10 normal subjects before and at the end of a 6-hr infusion of met-hGH. Five subjects were studied in the postabsorptive state and five were studied on the 10th day of intravenous repletion. Measurements of hormonal levels, serum amino acid levels, and free fatty acid levels, as well as extremity amino acid and free fatty acid fluxes, were performed. Met-hGH in the postabsorptive setting had no effect on extremity amino acid flux but significantly increased extremity free fatty acid efflux. In contrast, met-hGH in the background of intravenous feeding produced a significant extremity uptake of total amino acids but had no effect on free fatty acid flux. These data suggest a relationship between the substrate background and the actions of met-hGH on both peripheral protein and lipid metabolism. Therefore, the adequacy and composition of the feeding regimen may be important when considering growth hormone as an adjunct to nutritional therapy.

Adult↗
PubMed1992

Metabolic regulation in peripheral tissues and transition to increased gluconeogenic mode during prolonged exercise.

To assess the means by which peripheral metabolism facilitates the transition to a gluconeogenic state, dogs were studied during 150 min of moderate treadmill exercise. Metabolism in the working hindlimb was assessed with arteriovenous difference and isotopic techniques (n = 9). In a separate group (n = 6), hepatic metabolism was assessed using arteriovenous differences. Limb glucose uptake (LGU) and oxidation (GOX) rose from 33 +/- 10 and 5 +/- 2 to 101 +/- 20 and 54 +/- 15 mumol/min at 10 min of exercise. LGU continued to rise (151 +/- 21 mumol/min at 150 min), while GOX declined. Nonoxidative glucose metabolism (GNOX) was 28 +/- 10 mumol/min at rest and 47 +/- 24 and 108 +/- 16 mumol/min at 10 and 150 min of exercise. Limb nonglycemic (predominantly glycogen) pyruvate formation rose from 52 +/- 22 to 198 +/- 54 and 242 +/- 74 mumol/min at 10 and 150 min of exercise. The gradual increase in GNOX and the high glycogenolytic rate were paralleled by accelerated lactate, pyruvate, and glutamine releases. Limb glycerol release rose promptly and remained elevated during exercise. Plasma nonesterified fatty acids (NEFAs) rose gradually and paralleled the gradual rise in GNOX (r = 0.93). The resulting rise in hepatic NEFA delivery was highly correlated to hepatic O2 uptake (r = 0.87), hepatic vein lactate-to-pyruvate ratio (r = 0.90), and intrahepatic gluconeogenic efficiency (r = 0.96). In summary, during exercise, 1) the primary fate of the added glucose consumed by the working limb is initially oxidation, but becomes GNOX as exercise duration progresses; 2) glycogenolysis rises promptly, but attains its highest rate at the end of exercise; 3) the late increases in GNOX and glycogenolysis relate to an increased gluconeogenic precursor release from the working limb; 4) although lipolysis increases promptly and is sustained, circulating NEFAs rise only gradually; and 5) the gradual rise in plasma NEFAs is highly correlated to the shift from GOX to GNOX and the adjustments in hepatic metabolism that are necessary for the full gluconeogenic response.

Amino Acids↗
PubMed1975

Metabolism and mode of action of androgens in target tissues of male rats. V. Uptake and metabolism of cyproterone acetate and its influence on the uptake and metabolism of testosterone and 5alpha-dihydrotestosterone in target organs and peripheral tissues.

In order to get more information on the mode of action of anti-androgens, two series with low but biologically active doses of cyproterone acetate were started. In the first experiments 12 mug of [3H]cyproterone acetate was injected intravenously into adult rats castrated 3 days before treatment. Thirty min after injection the radioactivity uptake in the target organs and other tissues was measured. The metabolites were separated by thin layer chromatography. A large pool of radioactivity could be shown in the liver. Thin layer chromatography revealed that in this pool cyproterone acetate had been converted by more than 80% to one metabolite. In blood plasma, too, the metabolite accounted for the major part of radioactivity. When compared to skeletal muscle, the prostate, seminal vesicles, and m. bulbocavernosus and m. levator ani accumulated more radioactivity. Within 30 min unchanged cyproterone acetate was retained selectively thus showing its relative high affinity to target organs. In a second experimental series, adult castrated male rats were given 10 mug of cyproterone acetate intravenously 30 min before the injection of [3H]testosterone or [3H]5alpha-dihydrotestosterone. Under this condition androgen uptake in target tissues was reduced to about 70% of the control values. The data parallel the results of in vivo studies on cytosol receptor displacement of androgens by cyproterone acetate. In agreement with previous investigators no significant influence of the anti-androgen on androgen metabolism was observed. The importance of the findings concerning the mode of anti-androgen action is discussed.

Adipose Tissue↗
PubMed1988

ANF receptors: distribution and regulation in central and peripheral tissues.

Atrial natriuretic factor is a recently-discovered family of biologically active peptides produced in, stored and secreted by mammalian atria. ANF exerts a wide variety of actions in the periphery as well as within the central nervous system. In general, these actions are directed toward the maintenance of body fluid and electrolyte balance and regulation of arterial blood pressure. In a fashion similar to that of many other hormonal systems, the actions of ANF in various target tissues appear to be mediated by at least one class of specific receptors. However, while the biosynthesis and biological actions of ANF have been extensively investigated, little research has been focused on ANF receptor systems. In this article, we will provide an overview of current literature regarding the distribution and binding characteristics of receptor sites for ANF in peripheral and central target tissues. In addition, we will consider factors involved in the regulation and alteration of ANF receptor sites in various tissues. Finally, a brief discussion of the emerging concept of ANF and angiotensin II as mutual antagonists in body fluid homeostasis and cardiovascular regulation will be offered.

Animals↗
PubMed1995

Vitamin E in macular and peripheral tissues of the human eye.

This study was undertaken to investigate the distribution of vitamin E in the macular and peripheral regions of the human retina, retinal pigment epithelium (RPE) and choroid as a function of age. High-performance liquid chromatography (HPLC) was used to measure alpha- and gamma-tocopherol levels quantitatively using tocol as an internal standard. In 57 out of 70 donor eyes (ages 9-104) the macular region was isolated and the tocopherols analyzed. The conventional brush method and a new vortex method were used to isolate the retinal pigment epithelium cells. Similar trends for the vitamin E levels (increase to the 5th decade, decrease after 7th decade) were found for the macular and peripheral retina and for the macular RPE. In the peripheral RPE a slight continuous increase with age was found. The vitamin E levels are higher in the RPE than in the retina, for both macular and peripheral regions. The amounts of vitamin E/mg protein are lower in the macular retina than in the peripheral retina, whereas in the RPE there is no difference in vitamin E content between macular and peripheral regions. A simple method based on a gentle vortex step was found to offer several advantages over the more generally used isolation of RPE cells based on brushing, and there was no difference in recovery of vitamin E in RPE cells when they were isolated by either isolation technique. It was also found that denominators, used to express the values of vitamin E in tissues should, be used with care since age dependent trends in parameters/denominators could be caused by trends in the denominators only.

Adolescent↗
PubMed1990

Fetal nicotine exposure produces postnatal up-regulation of adenylate cyclase activity in peripheral tissues.

Gestational exposure to nicotine has been shown to affect development of noradrenergic activity in both the central and peripheral nervous systems. In the current study, pregnant rats received nicotine infusions of 6 mg/kg/day throughout gestation, administered by osmotic minipump implants. After birth, offspring of the nicotine-infused dams exhibited marked increases in basal adenylate cyclase activity in membranes prepared from kidney and heart, as well as supersensitivity to stimulation by either a beta-adrenergic agonist, isoproterenol, or by forskolin. The altered responses were not accompanied by up-regulation of beta-adrenergic receptors: in fact, [125I]pindolol binding was significantly decreased in the nicotine group. These results indicate that fetal nicotine exposure affects enzymes involved in membrane receptor signal transduction, leading to altered responsiveness independently of changes at the receptor level.

Adenylyl Cyclases↗
PubMedDate not supplied

The use of topical nitroglycerin ointment to treat peripheral tissue ischemia secondary to arterial line complications in neonates.

Catheterization of the aorta through the umbilical artery and/or of peripheral arteries in neonates may be accompanied by a number of complications, of which thrombotic phenomena and peripheral vasospasm are the most common. Two neonates with peripheral ischemia caused by vasospasm from indwelling umbilical artery catheterization and one infant with left hand ischemia due to a left radial artery line were successfully treated with 2% nitroglycerin ointment. No adverse effects were noted.

Catheterization, Peripheral↗
PubMed1996

Splanchnic and peripheral tissue perfusion in experimental fat embolism.

OBJECTIVE: To investigate the acute effects of experimental fat embolism on splanchnic and peripheral perfusion and oxygenation in pigs. DESIGN: Randomized, controlled trial. SETTING: Animal laboratory. SUBJECTS: Eighteen domestic pigs, weighing 25 to 31 kg. INTERVENTIONS: The 18 pigs were randomized to either the fat embolism or control groups. Nine anesthetized and mechanically ventilated pigs were intracavally infused with a 10% allogeneic bone marrow suspension at a dose of 100 mg/kg over 5 mins (the fat embolism group); nine control pigs received normal saline in the same volume and speed (control group). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary shunt increased, and PaO2 decreased immediately after the bone marrow suspension infusion. In the fat embolism animals, oxygen delivery decreased, oxygen content difference widened, and total oxygen consumption remained high, indicating enhanced oxygen extraction. Further, superior mesenteric artery blood flow and mesenteric oxygen delivery decreased, while intramucosal pH in the small bowel was stable. Subcutaneous PO2 decreased in both groups, whereas transcutaneous PO2 decreased only in the animals receiving bone marrow suspension. Skin red cell flux showed no significant changes. CONCLUSIONS: The present model of fat embolism results in significant impairment in systemic oxygenation. Despite this fact, the intestinal oxygenation remains unaffected probably due to sufficient compensatory mechanisms. Transcutaneous PO2 measurements may provide a useful index for early detection of fat embolism.

Animals↗
PubMed1980

Effect of steroids on vasoactive intestinal peptide in discrete brain regions and peripheral tissues.

The effect of castration and adrenalectomy was studied on vasoactive intestinal peptide (VIP) concentrations in various brain and peripheral structures of male rats. Castration has no effect on any of the structures studied, whereas 4 weeks adrenalectomy (ADX) decreases VIP concentrations in the hippocampus and increases them in the adenohypophysis, two structures known to contain large amounts of glucocorticoid receptors. Corticosterone administration restores VIP levels to control values only in the dorsal hippocampus. In contrast, dexamethasone counteracts both the decrease and the increase of VIP concentrations obtained after ADX in the hippocampus and in the adenohypophysis respectively. The present results suggest that corticosteroids can be involved in the regulation of VIP actions both in the brain and in the adenohypophysis.

Adrenalectomy↗
PubMed1994

Effects of systemic infusions of endotoxin, tumor necrosis factor, and interleukin-1 on glucose metabolism in the rat: relationship to endogenous glucose production and peripheral tissue glucose uptake.

This study was performed to characterize and compare the actions of insulin on hepatic glucose production and peripheral glucose utilization during infusions of endotoxin, tumor necrosis factor (TNF), interleukin-1 (IL-1), and a combination of IL-1 and TNF in the rat. The euglycemic hyperinsulinemic clamp technique was combined with a primed-constant tracer infusion of high-performance liquid chromatography (HPLC)-purified 3H-3-glucose for estimation of whole-body glucose appearance and utilization rates; 14C-deoxyglucose (14C-DG) uptake was also measured in specific tissues following intravenous bolus administration. As expected, acute endotoxemia resulted in a significant reduction of glucose infusion during the clamp procedure (insulin concentration, 100 microU/mL), suggesting decreased insulin action. Similarly, infusion of TNF decreased the rate of glucose infusion necessary to maintain euglycemia. However, differences between endotoxin- and cytokine-treated rats were noted in whole-body glucose appearance (or disappearance) rates. Whereas endotoxin infusion predominantly decreased whole-body glucose uptake, suggesting diminished utilization in skeletal muscles, cytokine infusions were associated with a measurable hepatic glucose output despite hyperinsulinemia. In contrast, both cytokine and endotoxin administration decreased the rate of 14C-DG uptake by muscle tissue. These results demonstrate that TNF, IL-1, and endotoxin can induce a state of insulin resistance when infused continuously; the results also emphasize the complexity of regulation of glucose homeostasis during infection and sepsis.

Animals↗
PubMed1993

Plasma 5-hydroxyindoleacetic acid as an indicator of monoamine oxidase-A inhibition in rat brain and peripheral tissues.

We have examined the changes induced by the monoamine oxidase (MAO; EC 1.4.3.4) inhibitors tranylcypromine, clorgyline, and deprenyl on MAO activity and 5-hydroxytryptamine (serotonin, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in rat brain and blood (plasma and whole blood). The decreases of MAO-A activity observed in the liver and lungs after different doses of clorgyline or tranylcypromine correlated significantly (r > 0.80 in all cases) with the decline of plasma 5-HIAA. This was unaffected by 0.25 and 5 mg kg-1 of deprenyl, indicating that 5-HT was deaminated exclusively in the periphery by MAO-A. It is interesting that very potent and significant correlations (r > 0.75) were found between plasma 5-HIAA and MAO-A activity, 5-HIAA and 5-HT content in brain tissue. These results suggest that plasma 5-HIAA can be used confidently as a peripheral indicator of the inhibition of MAO-A in brain. This may represent a favorable alternative to the analysis of 5-HIAA in CSF in psychiatric patients undergoing antidepressant treatment with nonspecific MAO inhibitors or with the new selective MAO-A inhibitors.

Animals↗