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M Koulu

Publications and source records attributed to M Koulu.

106 records · Page 6Linked to original sources
PubMed1985

Neuroendocrine aspects in monitoring of dopaminergic drugs in man.

The role of plasma homovanillic acid together with serum growth hormone and prolactin in monitoring of central dopaminergic activity was studied in healthy volunteers and psychiatric patients. Both dopaminergic agonists (apomorphine, bromocriptine and L-dopa) and antagonists (metoclopramide) were used. Apomorphine, bromocriptine and metoclopramide, which exerted the expected neuroendocrine effects caused no significant changes in plasma homovanillic acid. L-dopa increased the concentration of homovanillic acid in plasma. This effect was not potentiated by L-deprenyl, although L-dopa-induced growth hormone secretion was increased after L-deprenyl premedication. There was negative correlation between growth hormone secretion and the increase of plasma homovanillic acid after L-dopa. This indicates that the L-dopa-induced rise in plasma homovanillic acid probably reflects more peripheral L-dopa metabolism than central dopaminergic activity. Thus, it seems that plasma homovanillic acid cannot be regarded as a sensitive indicator of drug-induced changes in central dopaminergic activity in man, which is in contrast with some earlier findings in animals.

Apomorphine↗
PubMed1984

Determination of conjugated dopamine in cerebrospinal fluid from humans and non-human primates with high performance liquid chromatography using electrochemical detection.

A simple and reliable procedure for the determination of conjugated dopamine (DA) in cerebrospinal fluid (CSF) is described. The conjugate, presumably a sulfate, is conveniently hydrolyzed in 0.4 M sulfuric acid at 95 degrees. Thereafter, dopamine is quantitated using HPLC with electrochemical detection. Sensitivity (0.5 pmol/ml) is sufficient for clinical studies. Only 400 ul of CSF are required for the assay. The within assay coefficient of variation was 3.2% for conjugated DA (concentration of 11.8 pmol/ml). In a material consisting of 261 samples of lumbar CSF from unmedicated psychiatric patients and normal control subjects, a concentration range of 1.3-21.7 pmol/ml was found. No clear differences were evident between the major diagnostic groups.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Human growth hormone and dopaminergic drugs, with special reference to deprenyl (selegiline): a summary of studies on volunteers.

The tubero-infundibular dopaminergic tract of the hypothalamus has a stimulatory effect on growth hormone (GH) secretion. In healthy volunteers levodopa, through the released dopamine and direct dopamine receptor agonists, therefore induces transient GH secretion. The indirect effect of levodopa at the presynaptic level can be modulated by inhibitory GABAergic drugs and by the potentiating deprenyl, for example. The GH response to direct postsynaptic dopamine receptor agonists like apomorphine is unaffected by these modulators. Below the dopamine level, the inhibitory effect of somatostatin and the negative feedback of the GH itself come into play. These regulatory mechanisms place limitations on dopamine-GH studies in man.

Apomorphine↗
PubMed1983

Effect of the benzodiazepine derivative, diazepam, on the clonidine-stimulated human growth hormone secretion.

gamma-Aminobutyric acid (GABA) has both stimulatory and inhibitory effect on human GH secretion. We previously reported that the benzodiazepine derivative diazepam, which exerts its main pharmacological effect by facilitating GABA-mediated transmission, is able to reduce the GH response to L-dopa and apomorphine. To establish whether diazepam affects the alpha-adrenergic regulation of GH secretion, the GH response to clonidine (an alpha-agonist) was investigated in seven volunteers after placebo and diazepam premedications. After placebo pretreatment, clonidine (0.15 mg iv infused over 20 min) significantly stimulated GH secretion: the mean serum GH level rose from a basal level of 4.7 +/- 1.1 (+/- SEM) ng/ml to a maximum of 10.8 +/- 1.6 ng/ml (P less than 0.025). After 3 days of diazepam treatment, a similar GH response to clonidine was observed; the mean serum GH level rose from a basal value of 2.3 +/- 0.3 ng/ml to a maximum of 9.4 +/- 1.3 ng/ml. It is concluded that the inhibitory effect of diazepam on human GH secretion is mediated via inhibition of dopaminergic transmission, whereas the alpha-adrenergic control of GH release is not affected. Since diazepam potentiates GABAergic transmission, its effect may reflect the role of endogenous GABA in human GH secretion.

Adult↗
PubMed1981

Effects of L-deprenyl on human growth hormone secretion.

The effects of L-deprenyl on L-dopa-, apomorphine- and L-tryptophan-induced growth hormone (GH) secretion were studied in thirteen healthy male volunteers. An acute 10 mg dose of L-deprenyl did not stimulate the basal GH secretion. Short-term L-deprenyl premedication significantly enhanced the L-dopa-stimulated GH release. In contrast, L-deprenyl premedication did not change the GH response to apomorphine or L-tryptophan. Potentiation of L-dopa-induced GH release by L-deprenyl indicates an increased availability of dopamine at the receptor level without a direct agonistic effect by the drug. Furthermore, L-deprenyl does not change the function of postsynaptic dopamine receptors involved in human GH release.

Adult↗
PubMed1981

Pharmacokinetics of dihydroergotamine in healthy volunteers and in neurological patients after a single intravenous injection.

The pharmacokinetics of dihydroergotamine (DHE) was studied in healthy volunteers (n = 6) and in neurological patients (n = 12). After a single 1.0 mg intravenous injection (n = 5) DHE quickly disappeared (T 1/2 beta = 32.9 min, Vdss = 0.33 liter/kg, Cltot = 1055.7 ml/min). In saliva (dose 1.0 mg, n =6) and cerebrospinal fluid (dose 0.5 mg, n =12) there were no measurable amounts of DHE after a single i.v. dose. The 32-h cumulative urinary excretion was 0.02-0.04% of the 1.0 mg intravenous dose. In one subject renal (0.18 ml/min) and extrarenal (692.9 ml/min) clearance of DHE was calculated. According to our results DHe is probably eliminated mainly by hepatic metabolism. The pharmacokinetic properties of DHE indicate a fast clinical response without a cumulative action.

Adult↗
PubMed1979

The effect of methysergide, pimozide, and sodium valproate on the diazepam-stimulated growth hormone secretion in man.

Diazepam-induced GH secretion was tested on 28 male volunteers before and after a 3-day treatment with methysergide, pimozide, or sodium valproate. Serum GH, diazepam, and blood glucose levels were determined. Without prior medication, the mean serum GH level increased 336% 1 h after diazepam administration. Treatment with the serotonin antagonist, methysergide, had no effect on the diazepam-stimulated GH secretion, whereas pimozide, the selective dopamine receptor-blocking agent, reduced the GH response to diazepam by 50% (P less than 0.05). Sodium valproate, a gamma-aminobutyric acid transaminase inhibitor, also inhibited diazepam-induced GH secretion; stimulated GH levels were 51% at 30 min (P less than 0.025), 39% at 60 min (P less than 0.025), and 46% at 90 min (P less than 0.025) relative to the stimulated levels without medication. No difference was found in blood glucose or serum diazepam levels after the drug treatments relative to the values obtained under basal conditions. It is suggested that diazepam-induced GH secretion is at least partly mediated via dopaminergic mechanisms. Serotonin does not seem to be involved. It is further proposed that gamma-aminobutyric acid plays an inhibitory role in GH secretion.

Adult↗
PubMed1979

Stimulatory effect of acute baclofen administration on human growth hormone secretion.

The effect of acute administration of the gamma-amino-butyric acid (GABA) derivative, baclofen, on human GH secretion was tested. In eight of the nine volunteers, both 5 and 10 mg baclofen (Lioresal) significantly basal GH secretion. Previoulsy, it has been reported that subacute baclofen treatment inhibits the GH response to insulin hypoglycemia and arginine. Thus, the present study shows that baclofen is able to modify GH secretion via different mechanisms, depending on the test situation and duration of treatment. As a putative GABA agonist, the effect of baclofen may be mediated via GABA-ergic pathways. Because of variable results, the evaluation of a possible physiological role of GABA in GH secretion requires further study.

Aminobutyrates↗
PubMed1979

Effect of melatonin on L-tryptophan- and apomorphine-stimulated growth hormone secretion in man.

The effect of subacute melatonin (250 mg every 8 h over a period of 40 h) and placebo treatment on L-tryptophan- and apomorphine-stimulated GH secretion was tested in 13 volunteers. Melatonin premedication significantly reduced the GH response to peroral L-tryptophan loading, suggesting that melatonin affects GH secretion in man by interfering with serotonergic transmission. In the apomorphine test, no significant difference in GH response was observed after melatonin when compared to placebo treatment. This suggests that dopaminergic mechanisms do not have a central role in mediating actions of melatonin on the hypothalamic-pituitary axis. It is further proposed that melatonin influences GH secretion at a suprahypophyseal level.

Adult↗
PubMed1979

Alpha- and beta-adrenoceptor blocking properties of labetalol in renin release.

The effect of labetalol, an alpha- and beta-adrenergic receptor blocking antihypertensive, on plasma renin activity (PRA) and the hemodynamics of healthy volunteers at rest and during an ergometric exercise test was studied. Oral doses of 200 and 400 mg labetalol were tested against a placebo in a crossover manner. The labetalol plasma concentrations were determined. Systolic and diastolic blood pressures in the supine position decreased after 400 mg labetalol as did the response of the heart rate to exercise. The lower dose decreased the resting heart rate, but had no effect on the heart rate during exercise. The ergometric exercise induced an increase in PRA which was partly inhibited after 200 mg labetalol in a manner similar to that induced by beta-blockers in our earlier studies. After 400 mg labetalol PRA was already increased at one hour at sitting rest and this higher basal level was maintained for four hours. After this higher dose of labetalol the reaction of PRA to exercise was not significantly inhibited. In renin release the vasodilating alpha-blockade thus dominated the beta-blocking property of labetalol at the dose which decreased the blood pressure.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Hypothalamic monoamines and food intake in alcohol-preferring AA and alcohol-avoiding ANA rats.

The concentrations and synthesis of monoamines in various hypothalamic nuclei and the influence of monoaminergic drugs on food intake were studied in two rat lines produced by selective outbreeding for voluntary high and low alcohol drinking. The hypothalamic nuclei of the alcohol-preferring AA rats contained slightly more serotonin than those of the alcohol-avoiding ANA rats, but the accumulation of 5-hydroxytryptophan after inhibition of aromatic amino acid decarboxylase was the same in both lines. There was no significant difference in the basal concentrations of catecholamines between the lines, but the accumulation of L-DOPA was significantly greater in the ANA than the AA rats, suggesting differences in catecholamine turnover. This difference was significant in the paraventricular nucleus, which is involved in the regulation of food intake. Clonidine (an alpha 2-agonist) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) induced hyperphagia and 1-(3-trifluoromethylphenyl)piperazine (TFMPP, a 5-HT1B agonist) induced hypophagia dose-dependently in both rat lines. Clonidine tended to be more potent in the ANA than the AA rats. Food intake following a 20-h fast was significantly lower in the ANA than AA rats. These results suggest that the alcohol-avoiding ANA and alcohol-preferring AA rats have different hypothalamic monoamine mechanisms controlling food intake, which could also partially account for their differential alcohol acceptance.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Effect of a single lethal dose of TCDD on the levels of monoamines, their metabolites and tryptophan in discrete brain nuclei and peripheral tissues of Long-Evans rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent anorexigens in rats with a yet unidentified mechanism of action. Since biogenic amines are known to essentially participate in the control of body weight and food intake, their levels were determined in various hypothalamic and other brain sites together with selected peripheral tissues after TCDD administration to adult male Long-Evans rats. Rats were given a single lethal dose of TCDD (1000 micrograms/kg intraperitoneally, in dimethylsulphoxide) or vehicle alone and they were decapitated at 1, 5, 25 hr or 8 days after TCDD administration. The samples were analyzed for concentrations of biogenic amines and their metabolites by HPLC-EC. Administration of TCDD increased the concentration of tryptophan at 8 days after exposure by about 20% in almost all nuclei examined, with the change reaching statistical significance in the lateral hypothalamic area and in lateral and medial accumbens nuclei. Importantly, this elevation was not seen in pair-fed control animals. Although not statistically significant, there was a tendency to 5-10% diminished dopamine, serotonin and/or 5-hydroxyindoleacetic acid levels in most brain sites during the first day postexposure. The present results argue against a crucial role for catecholamines as mediators of TCDD toxicity. However, the delayed changes in brain tryptophan do not appear to be secondary to TCDD hypophagia.

Adrenal Glands↗
PubMedDate not supplied

Effect of subchronic metformin treatment on macronutrient selection in genetically obese Zucker rats.

Metformin has been particularly recommended to be used in obese type 2 diabetic patients because of its weight decreasing and serum lipid profile normalizing effects. In the present study the effects of subchronic metformin treatment on macronutrient selection, weight gain and plasma insulin and glucose were investigated in 20 genetically obese male Zucker rats which were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Half of the rats were given metformin hydrochloride 320 mg/kg/day up to 18 days in drinking water. The other half of the animals received normal drinking water as a control. Metformin treatment significantly reduced 24 hr carbohydrate (P < 0.01), fat (P < 0.001) and protein (P < 0.01) intake. The proportion of fat of the total consumed energy was significantly increased by metformin (P < 0.01) while the proportion of protein was decreased (P < 0.05). In hunger stimulated feeding experiment metformin decreased selectively protein intake (P < 0.01). Changes in macronutrient selection were associated with reduced body weight gain in metformin treated rats (P < 0.001). Metformin markedly reduced the hyperinsulinaemia (P < 0.01) and plasma glucose levels (P < 0.05), which suggests improved glucose tolerance after metformin treatment. It is concluded that subchronic metformin treatment can modify the composition of energy intake in a macronutrient selective manner.

Animals↗
PubMedDate not supplied

Effect of chronic treatment with ICI D7114, a selective beta 3-adrenoceptor agonist, on macronutrient selection and brown adipose tissue thermogenesis in Sprague-Dawley rats.

ICI D7114 is a selective beta 3-agonist which stimulates brown adipose tissue thermogenesis. In the present study the effects of 18 days treatment with ICI D7114 (2 mg/kg/day orally) on macronutrient selection and brown adipose tissue thermogenesis were investigated in Sprague-Dawley rats. The rats were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Treatment with ICI D7114 did not change the macronutrient selection or total calories consumed by the rats. To monitor the thermogenic activation of brown adipose tissue the binding of [3H]GDP to brown adipose tissue mitochondria was measured. The treatment with ICI D7114 increased the binding of GDP both when expressed as total binding per lobe (P < 0.001) and per mg of protein (P < 0.01). It is concluded that ICI D7114, used in doses affecting brown adipose tissue thermogenesis, does not change the macronutrient selection or total energy intake in Sprague-Dawley rats.

Adipose Tissue, Brown↗