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L Hedler

Publications and source records attributed to L Hedler.

At least 37 records · Page 2Linked to original sources
PubMed1981

Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers.

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 micrometer cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 micrometer), alpha-methyl-noradrenaline (0.01-0.1 micrometer), xylazine (0.1-10 micrometer) and guanabenz (0.01 micrometer) decreased, whereas yohimbine (0.01-1 micrometer), rauwolscine (0.01-1 micrometer), corynanthine (10 micrometers), tolazoline (0.1-10 micrometers) and azapetine (0.1-1 micrometer) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 micrometer did not change the evoked overflow, and a higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolscine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the alpha-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the alpha-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with alpha-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the alpha 2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be alpha 2.

Animals↗
PubMed1981

Effect of prostaglandins D2, E2 and F2alpha on catecholamine release from slices of rat and rabbit brain.

Slices of rabbit or rat brain cortex were preincubated with [3H]noradrenaline, and slices of rabbit caudate nucleus or rat stratum with [3H]dopamine. The slices were then superfused and stimulated electrically. In rat cortex slices, PGE2 (0.01-1 millimicronmol/l) markedly reduced the stimulation-evoked overflow of tritium. PGF2alpha (1 millimicronmol/l) caused a slight decrease only after the formation of endogenous prostaglandins had been blocked by indomethacin. PGD2 (1 millimicronmol/l) had no effect. In slices of rabbit cortex and caudate nucleus as well as in rat striatal slices, none of the prostaglandins (1 millimicronmol/l) caused any change, irrespective of whether the production of endogenous prostaglandins was intact or blocked. The results show that, of three major prostaglandins that occur in the brain, only PGE2 is a potent presynaptic inhibitor of noradrenaline release in the rat. The catecholamine neurones of rabbit brain, and the dopamine neurones of rat striatum, are resistant to these prostaglandins.

Animals↗
PubMed1981

Metabolism of endogenous and exogenous noradrenaline in guinea-pig atria.

The outflow of noradrenaline, 3, 4-dihydroxy-phenylglycol (DOPEG) and 3, 4-dihydroxymandelic acid (DOMA) from guinea-pig isolated atria was studied by chromatography on alumina followed by high pressure liquid chromatography with electrochemical detection. In the absence of drugs, the outflow of endogenous noradrenaline over a period of 3 h averaged 1.6 pmol x g-1 x min-1 and the outflow of DOPEG 17 pmol x g-1 x min-1. The outflow of DOMA was below the detection limit (less than 0.31 pmol x g-1 x min-1). Tyramine greatly increased the outflow of noradrenaline and DOPEG, and the reserpine-like compound Ro4-1284 selectively increased the outflow of DOPEG; DOMA remained below the detection limit. When atria were exposed to (-) noradrenaline 1.7 or 17 microM, the subsequent outflow of noradrenaline and DOPEG was enhanced. Moreover, substantial amounts of DOMA were now found. This outflow of DOMA was prevented when atria were exposed to (-) noradrenaline in the presence of cocaine or after an initial incubation with amezinium. Exposure to (-)-noradrenaline 1.7 microM mainly enhanced the formation of DOPEG, while exposure to (+)-noradrenaline 1.7 microM mainly enhanced the formation of DOMA. Our experiments confirm some and qualify other conclusions drawn from studies in which exogenous 3H-noradrenaline had been used to examine the metabolism of noradrenaline in guinea-pig atria. In agreement with the isotope studies, DOPEG is a major metabolite of endogenous noradrenaline. In contrast to what the isotope studies had suggested, however, endogenous DOMA is a very minor product, at least as long as the neurones are at rest. DOMA is only formed when the tissue is exposed to high concentrations of exogenous noradrenaline. In further contrast to previous conclusions, DOMA is then formed intra- and not extraneuronally.

Animals↗
PubMed1976

The relation between the determinable quantities of volatile N-nitroso compounds and the peroxide number in soya bean oil.

Comparative studies of soya bean oil with and without addition of N-nitroso compounds (NDMA and NDEA) at different hydroperoxide concentrations have shown that the determinable quantities of substances having the retention time of N-nitroso compounds in soya bean oil and of nitrosoamines added to the oil are dependent upon the peroxide number. The determination was carried out by gas chromatography (nitrogen detector, nitrogen-sensitive, flame-ionization detector) prior to and following irradiation with UV light (360 nm). When the peroxide number was above 4, the determinability and the recovery were reduced by more than 60 per cent. In advanced autoxidation and after reduced recoveries, large amounts of NMDA and NDEA may be encountered for a short time. A possible linkage between N-nitroso compounds and peroxide is discussed. Comparative investigations of soya beans, crude oil, intermediates and commercially available steamed oils have revealed that the concentrations of the compounds with NDMA and NDEA properties in crude oil (peroxide number about 3) is higher than in soya beans. The recovery of these compounds is very poor in intermediate products with high peroxide numbers (about 5 to 9). However, N-nitroso compounds can be demonstrated in commercially available oils treated with steam (peroxide number about 0.7), although to a lesser extent than in crude oil.

Chemical Phenomena↗
PubMedDate not supplied

Effects of alpha 1- and alpha 2-adrenoceptor blocking drugs on noradrenaline release rate in anesthetized rabbits.

[3H]noradrenaline was infused intravenously into pentobarbitone-anesthetized rabbits to reach a steady-state plasma (3H]noradrenaline level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was determined simultaneously, and the rate of noradrenaline release was then derived. The effects of a series of selective alpha 1- and alpha 2-adrenoceptor blocking drugs on the noradrenaline release rate and noradrenaline clearance were investigated. Yohimbine (1 mg/kg i.v.), rauwolscine (1 mg/kg i.v.), corynanthine (1 mg/kg i.v.), prazosin (0.3 and 1 mg/kg i.v.), phenoxybenzamine (4 mg/kg i.v.), and sodium nitroprusside (10 micrograms/kg/min i.v.) decreased the plasma noradrenaline clearance. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine, as well as phenoxybenzamine, increased the noradrenaline release rate more than equihypotensive doses of the directly acting vasodilators hydralazine and sodium nitroprusside. The selective alpha 1-adrenoceptor blocking drugs prazosin and corynanthine increased the noradrenaline release rate less than equihypotensive doses of the vasodilators. These results suggest that, in vivo, blockade of alpha 2-adrenoceptors results in increased noradrenaline release, probably due to blockade of inhibitory presynaptic alpha 2-adrenoceptors at sympathetic nerve endings. Blockade of alpha 1-adrenoceptors, on the other hand, appears to depress baroreceptor-mediated increases in noradrenaline release in response to a fall in blood pressure.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Local modulation of noradrenaline release in vivo: presynaptic beta 2-adrenoceptors and endogenous adrenaline.

Isoprenaline bitartrate (0.5 microgram/kg/min i.v.) increased the rate of noradrenaline release into the circulation of pentobarbitone-anesthetized rabbits. This increase was much greater than that produced by an equi-hypotensive dose of the vasodilator hydralazine (0.2 mg/kg i.v.), suggesting that it was only partly due to baro-reflex activation of sympathetic nerves. This facilitatory effect of isoprenaline was also observed in the nephrectomized, pithed rabbit, with electrically stimulated sympathetic outflow, ruling out central nervous system and renin-angiotensin effects. ICI 118,551 HCl (0.3 mg/kg + 0.1 mg/kg/h i.v.) blocked the isoprenaline-induced hypotension, but did not affect the isoprenaline-induced tachycardia, suggesting that it selectively blocked beta 2-adrenoceptors. ICI 118,551 totally abolished the isoprenaline-induced increase in noradrenaline release, suggesting a beta 2-effect. Atenolol (0.3 mg/kg + 0.1 mg/kg/h) blocked the isoprenaline-induced tachycardia, a beta 1-effect, but only slightly attenuated the isoprenaline-induced increase in noradrenaline release. Atenolol by itself decreased heart rate and arterial pressure, but there was no reflex rise in the noradrenaline release rate, which suggests that atenolol impairs baroreceptor activation of sympathetic nerves. In another series of experiments, also in the pentobarbitone-anesthetized rabbit, adrenaline was released into the circulation by splanchnic nerve stimulation. This resulted in prolonged increases of adrenaline levels in heart tissue. After the plasma adrenaline levels had returned to prestimulation values, the rate of noradrenaline release into the plasma was enhanced. This increase was not observed in rabbits treated with either desipramine HCl (1 mg/kg i.v.) or propranolol HCl (2 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗