Gamma-aminobutyric acid and chloride channels: regulation by neuropeptides.
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Animals↗
Biomedical subjects
H Alho
Publications and source records attributed to H Alho.
Microfluorimetric quantitation of catecholamine turnover in the sympathetic neurons of rat.
The quantitative aspects of the formaldehyde-induced fluorescence and the turnover of catecholamines in the sympathetic neuronal perikaryon of different sympathetic ganglia were studied after a blockade of the amine synthesis with alpha-methyltyrosine. The concentration of catecholamines was determined by microfluorimetric quantitation method. The half-life of catecholamines in sympathetic neuronal perikarya was short and depended on the ganglion studied. The turnover rate of catecholamines in sympathetic neurons was highest in superior cervical and lowest in coeliac ganglion. Brightly fluorescent fibers were still seen five hours after the amine synthesis blockade, whereas almost all cell bodies had lost their fluorescence. Also small intensely fluorescent cells were still brightly fluorescent after the follow-up period. Microfluorimetrically determined turnover of catecholamines gave more detailed information about the turnover of catecholamines in sympathetic nervous system when compared to the biochemical methods used earlier.
Animals↗
Histochemically demonstrable catecholamines in sympathetic ganglia and carotid body of spontaneously hypertensive and normotensive rats.
The catecholamine content and morphology of the superior cervical and the hypogastric ganglion and the carotid body were studied in Spontaneously Hypertensive Rats (SHR) before (at the age of 6 weeks) and after (at the age of 20 weeks) becoming hypertensive, with Wistar Kyoto (WKY) rats as controls. The study was performed by formaldehyde-induced fluorescence method combined with quantitative microfluorimetry of catecholamines. At the age of 6 weeks the only significant difference observed between the rat strains was a greater number of small intensely fluorescent (SIF) cells in the superior cervical ganglion of SHR. At the age of 20 weeks the fluorescence intensity was higher in the principal neurons of the superior cervical ganglion and in glomus cells of the carotid body of SHR compared to WKY. The volumes of superior cervical ganglion and carotid body were larger in 20-week-old SHR compared to WKY. In the hypogastric ganglion differences were not found between SHR and WKY rats. The present results show differences in the superior cervical ganglion and in the carotid body of adult SHR compared to controls. These differences develop during the time period when the SHR become hypertensive, and might be functionally significant in the regulation or maintenance of the increased blood pressure in SHR rats.
Animals↗
Effect of prolonged physical training on the histochemically demonstrable catecholamines in the sympathetic neurons, the adrenal gland and extra-adrenal catecholamine storing cells of the rat.
The effect of daily physical training for 24 months on the sympathetic neurons, adrenal gland, extra-adrenal catecholamine storing cells and on the heart was investigated in rats. The tissue catecholamine fluorescence intensity was determined by microfluorimetric quantitation of catecholamines. The maximal and final body weights were significantly lower in trained animals. The trained rats showed prominent increase of heart weight relative to body weight, while the adrenals did not enlarge. The adrenergic nerve fiber density of the heart and the fluorescence intensity of the terminal axons were significantly increased. There were no changes in the fluorescence intensity of the perikarya of the sympathetic neurons and the amount of extra-adrenal catecholamine storing cells after physical exercise. The volume of the superior cervical ganglion was doubled and the neuronal perikarya were enlarged in trained animals. The prolonged physical training throughout the life span of the rat gave new information about the reactions of the sympathetic nervous system to physical exercise.
Adrenal Medulla↗
Microfluorimetric quantification of catecholamine fluorescence in rat sympathetic ganglia.
The formaldehyde-induced fluorescence (FIF) technique was used to generate catecholamine fluorophores in the perikarya of the sympathetic neurons in the superior cervical ganglion of adult rats. During microfluorimetric quantification, the photodecomposition was eliminated by a rapid measuring procedure with a small excitation field and by using only visible light between the measurements. The catecholamine fluorescence, induced in protein microdroplets with increasing noradrenaline concentrations, was linear up to 2 X 10(-2) M which exceeds the noradrenaline content of even the most intensively fluorescent neurons. Thus, the differences in fluorescence intensities directly reflect the physiological state of each neuron with respect to their catecholamine content. The mean histograms reveal the changes which can only occur in certain neurons, and which can disappear if the mean only is assessed. The microfluorimetric method was sensitive enough to detect even minute changes induced by reserpine treatment in the catecholamine content of the sympathetic ganglion cells.
Animals↗
Localization of [Met5]- and [Leu5]-enkephalin-like immunoreactivity in nerve terminals in human paravertebral sympathetic ganglia.
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Adult↗
Electron-microscopic localization of enkephalin-like imnmunoreactivity in axon terminals of human sympathetic ganglia.
The peroxidase-antiperoxidase method was applied to demonstrate enkephalin-like immunoreactivity in the human sympathetic ganglia. A network of immunoreactive fibres was found in light microscopy between the nonreactive neurons. Electron microscopy showed immunostaining to be restricted to axonal profiles containing both large and small vesicles. The strongest reaction was associated with large vesicles.
Adult↗
Microspectrofluorimetric estimation of the formaldehyde-induced fluorescence of the developing main pelvic ganglion of the rat.
The formaldehyde-induced fluorescence (FIF) of the cytoplasm of individual developing neurons of the main pelvic ganglion was recorded microspectrofluorimetrically in order to follow changes in catecholamine (noradrenaline) content during development. For each ganglion, the fluorescence intensity profile was estimated and shown graphically as columns expressing percentage distribution of relative intensities in different intensity classes. During development, the number of weakly fluorescent neurons increases. Treatment with testosterone shifts the profile towards higher intensities in four- and six-week-old animals. Testosterone affected the main pelvic ganglion but not the superior cervical ganglion. The intensity of the cytoplasmic FIF, which correlates with the catecholamine (noradrenaline) content of the object tissue, showed a tendency to decrease during development. This change was not obvious vy visual observation because of the increase in cell size and the toal bulk of the ganglion. Other possible factors affecting visual observation are discussed.
Animals↗
Ultrastructure and histochemistry of human SIF cells and paraganglia.
The FIF method and electron microscopy were used to study SIF cells in the human sympathetic ganglia. In serial sections SIF cells in one ganglion often numbered less than 30, although they were found in every ganglion examined. Microspectrofluorimetry demonstrated the high catecholamine content in SIF cells. Electron microscopically these cells appeared as small granule-containing cells that receive a rich cholinergic type innervation. The diameter of the storage granules was 300 to 400 nm. In addition the SIF cells had close connections with each other. The SIF cells, situated solitary or as small clusters, were surrounded by satellite cells. Frequently the SIF cells located close to blood vessels.
Catecholamines↗
Microspectrofluorimetric quantitation of catecholamine fluorescence in rat SIF cells and paraganglia: effect of hypoxia.
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Animals↗
Small, intensely fluorescent cells of human sympathetic ganglia.
Human sympathetic ganglia obtained from sympathectomies were studied using the formaldehyde-induced fluorescence (FIF) method and electron microscopy to identify the small, intensely fluorescent (Sif) cells. Microspectrofluorimetry was used to study the intensity of the emitted FIF and the emission spectra. The SIF cells were found in every ganglion studied, but they were very sparce. They occurred alone or in small clusters and were mostly situated close to the blood vessels. The SIF cells contained high amounts of catecholamines, as indicated by microspectrofluorimetry. Electron microscopy revealed granule-containing cells (GC) enveloped by satellite cells; the former cells contained osmiophilic granules 300--400 nm in diameter and synapses of the cholinergic type were frequently found on their surface.
Dopamine↗
The distribution and endocrine nature of the abdominal paraganglia of adult man.
The paraganglia of adult man were studied using the formaldehyde-induced fluorescence (FIF) method for histochemical characterization of biogenic monoamines. Microspectrofluorimetry was used to record the emission spectra and fluorescence intensities of the paraganglionic cells. The study of samples from six patients showed that well vascularized paraganglia were widely distributed throughout the retroperitoneal spaces. The paraganglia exhibited strong FIF with the spectral characteristics of monamines. Treatment with HC1 caused an increase in the fluorescence intensity of the paraganglia and a simultaneous shift of the emission maximum from 480--495 nm. This change suggests the presence of high concentrations of tryptophyl-containing peptides and is not due to monoamines. The possibility of a dual endocrine function for the paraganglia is discussed.
Abdomen↗
Association between M/L55-polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with type 2 diabetes mellitus and in control subjects.
The paraoxonase enzyme (PON) gene polymorphism causes a change of methionine (M-allele) to leucine (L-allele). PON may reduce low density lipoprotein oxidation and prevent atherosclerosis. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive index of oxidative DNA damage. We have studied the association between the PON genotypes and the urinary excretion of 8-OHdG. The study population consisted of 93 Finnish type 2 diabetes patients and 106 non-diabetic control subjects. The 24-h excretion of 8-OHdG was significantly higher in diabetic patients than in control subjects (P < 0.001). In control subjects, the ratio of the 8-OHdG/glomerular filtration rate increased in order of genotype from MM to ML to LL (P < 0.0412). These results suggest that lipid peroxidation may have an effect on DNA oxidation.
8-Hydroxy-2'-Deoxyguanosine↗
Effects on endogenous acetaldehyde production by disulfiram and ethanol feeding on rat pancreas.
Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the pancreas in some isolated pancreas models, whereas in vivo such treatment has failed to induce pancreatitis. In vivo exogenous acetaldehyde may not be effective because it is rapidly metabolized. The aim of this study was to investigate whether endogenous acetaldehyde accumulates in the pancreas after ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, and whether this treatment can induce pancreatitis-like injury in the rat. The liver was studied for comparison. In part I of the experiment, adult male Wistar rats were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol plus disulfiram for 1 week (n = 24) or 3 weeks (n = 24) and for 3 weeks with (n = 6) and without (n = 6) hypovolemia. In part II of the experiment, rats were given water (n = 6), ethanol (n = 6), and high-dose disulfiram (n = 6) and ethanol plus high-dose disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood, liver, and pancreas were measured. Animal behavior was monitored, and weight changes, plasma amylase activity, water content, and histomorphology of the pancreas and liver were studied without knowing the group. No increases in plasma amylase activity and no histomorphologic changes in the pancreas were observed under light or electron microscopy in part I of the experiment. In part II, treatment with ethanol induced acetaldehyde accumulation in the liver (33.6 +/- 2.6 micromol/L), but to a lesser degree in the blood (9.6 +/- micromol/L) and pancreas (5.0 +/-.2 micromol/L). Ethanol plus disulfiram induced marked accumulation of acetaldehyde in the liver (83.2 +/- 15.9 micromol/L), blood (280.0 +/- 47.4 micromol/L), and pancreas (43.6 +/- 4.7 micromol/L). When tissue acetaldehyde levels reached 30 to 40 micromol/L, we found a decrease in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acinar cells and accumulation of lipid droplets in the hepatocytes, whereas physiologic signs of pancreatitis (hyperamylasemia, edema) or increases in liver enzymes did not develop. High levels of acetaldehyde accumulate in the liver and pancreas with the treatment described. Although this was accompanied by lipid degeneration of the hepatocytes and some subcellular changes in the acinar cells, physiologic signs of pancreatitis did not develop. Thus acetaldehyde accumulation alone, or in combination with hypovolemia, is not responsible for the induction of acute pancreatitis.
Acetaldehyde↗
Brief intervention for male heavy drinkers in routine general practice: a three-year randomized controlled study.
The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice. In five primary care out-patient clinics in a Finnish town, 296 male early-phase heavy drinkers consulting a general practitioner (GP) for various reasons were identified. Control group C (n = 88) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking. Groups A (n = 109) and B (n = 99) were offered in addition seven and three brief intervention sessions, respectively. All GPs took part, whether or not they indicated a special interest. The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption, mean corpuscular volume (MCV), and serum carbohydrate-deficient transferrin, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase. There were no statistically significant differences between study groups A, B and C in mean changes in outcome measures. Within all the groups, MCV decreased. Depending on the outcome measure used and the study group analysed, clinically significant reduction of drinking was found in 25-53% of the subjects. In routine general practice, giving additional sessions of brief intervention may not be as effective as in special research conditions. Factors reducing the effectiveness of brief intervention programmes should be investigated, so that primary health care staff can be better supported in their efforts.
Adult↗
Association of self-reported diseases and health care use with commonly used laboratory markers for alcohol consumption.
The relationships of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and their mathematical combination (gamma-CDT) with self-reported diseases were evaluated in a large cross-sectional risk factor survey. Significant gender effects were observed in associations of the markers with several medical conditions as well as with general health care utilization. In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was positively associated with hypertension and diabetes. gamma-CDT was positively associated with hypertension in males and with asthma in females. This general population study demonstrates that these markers, although most commonly used to assess alcohol misuse, might also serve as health risk indicators.
Adult↗
Cellular and subcellular localization of an octadecaneuropeptide derived from diazepam binding inhibitor: immunohistochemical studies in the rat brain.
Immunocytochemical methods, both light and electron microscopic, were used to identify the cellular and subcellular locations of octadecaneuropeptide-like immunoreactivity (ODN-LI) in rat brains serially sectioned in total. ODN-LI includes a newly discovered family of rat brain neuropeptides that are processing products of a common endogenous neuropeptide precursor, diazepam binding inhibitor (DBI). The members of this neuropeptide family have been shown to displace benzodiazepines and beta carbolines from their specific recognition sites located on the allosteric modulatory centers of GABAA receptors. We have previously examined the distribution of DBI-LI in rat brain. The anti-ODN antiserum used in this study does not cross-react with rat DBI, and thus allows a distinct analysis of ODN-LI as opposed to DBI-LI, in rat brain. Neuronal perikarya with ODN-LI were located in many brain nuclei, such as the pontine n., reticular thalamic n., subgeniculate n., supraoptic n. and suprachiasmatic n., and also in brain areas such as cerebral and cerebellar cortex, hippocampus, inferior colliculus, olfactory bulb and subiculum. In addition to perikaryal labelling, a punctate or diffuse immunostaining with ODN antibodies was detected in many brain regions such as cerebellum, hippocampus, amygdaloid area, olfactory tubercle, some of the deep cerebellar nuclei and some circumventricular organs. At the electron microscopic level ODN-LI was identified in neuronal perikarya, processes and terminals. In the axon terminals, ODN-LI appears to be associated with synaptic vesicles. Whenever ODN-LI was detected within neurons, DBI-LI was also found in identical cells. In addition to neurons, DBI-LI was found in glia or glial-like cells, while ODN-LI was not found in these cells. Our findings are consistent with the hypothesis that ODN may be a neuron-specific processing product of DBI and that ODN-like peptides may act as putative endogenous allosteric modulators of various GABAA receptor subtypes.
Animals↗