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Biomedical subjects

W Osswald

Publications and source records attributed to W Osswald.

At least 55 records · Page 3Linked to original sources
PubMed1980

The fate of isoprenaline after inhibition of O-methylation and of extraneuronal uptake.

In order to study the fate of isoprenaline in the presence of drugs which inhibit its extraneuronal uptake and O-methylation, strips of canine lateral saphenous veins strips were incubated for 60 min with 3H-isoprenaline (2 microM) in the presence of cortexone 60 microM and U-0521 100 microM. Cortexone reduced to about 50% the amount of 3H-isoprenaline accumulated in the presence of U-0521 and the addition of cocaine further reduced it by about 30%. Field stimulation of strips treated with cortexone and U-0521 resulted in the release of significant, although small, amounts of 3H-isoprenaline; this release was prevented by cocaine or by pretreatment with reserpine. Thus, when extraneuronal uptake and O-methylation are inhibited, isoprenaline behaves like a false transmitter. Even in the presence of cortexone, U-0521 and cocaine, a considerable amount of isoprenaline accumulates in the strips, presumably in non-muscular structures of the tunica media.

Animals↗
PubMed1978

Differences in the metabolic fate of noradrenaline released by electrical stimulation or by tyramine.

Strips of canine saphenous vein were loaded with 3H-noradrenaline (1.4 micrometer) and perifused with Krebs solution and either subjected to field stimulation or exposed to tyramine 40 micrometer. 3H, noradrenaline and its metabolites were determined in the perifusion fluid. Stimulation caused an increase predominantly in noradrenaline, followed by DOPEG, whereas tyramine release DOPEG in larger amounts than noradrenaline. Tyramine had more sustained effects than stimulation. Cocaine (1.6 micrometer) drastically reduced DOPEG efflux due to stimulation, but had no effects on the pattern of release by tyramine. It is concluded that tyramine releases noradrenaline which is deaminated before it reaches the synaptic gap, whereas after stimulation deamination of the transmitter occurs after re-uptake.

Animals↗
PubMed1976

Uptake, distribution and metabolism of isoprenaline in the dog saphenous vein.

Dog saphenous vein strips were incubated with 2 muM 3H-isoprenaline. After 2 and 8 min of incubation small cross sections were cut and prepared for light and ultrastructural autoradiography. In addition, the accumulation of 3H-isoprenaline (3H-ISO) in the tissue as well as the formation of 3-O-methylisoprenaline (3H-OMI) were determined by liquid scintillation counting. The density of silver grains was 6.5 times higher on smooth muscle than on connective tissue. It decreased from the intima to adventitia when determined in the 2 min specimens, suggesting the existence of a selective transport of isoprenaline through the endothelium of the vein. The preferential distribution into the juxta-intimal part of the media which was observed after the 2 min incubation period was abolished by cortexone. Silver grain density, especially over the smooth muscle, was markedly increased by U-0521 and decreased by cortexone. Simultaneous treatment with cortexone and U-0521 led to a marked accumulation of silver grains over neuronal tissue; this accumulation was prevented by cocaine. Strips incubated at 0 degrees C and without oxygen showed almost no grains. In control conditions the saphenous vein strips removed 1968 +/- 19 pmoles-g-1 during 8 min of incubation. 86.3% of that value corresponded to 3H-OMI formation. O-methylation of 3H-ISO was strongly inhibited by U-0521 and, in a lesser degree, by cortexone. The influence of U-0521 on inhibition of O-methylation of 3H-ISO was not modified by cortexone. We found a linear correlation between silver grain densities per unit area of the vein strips and the 3H-isoprenaline accumulation determined by liquid scintillation counting, indicating a clear correspondence between silver grains and 3H-isoprenaline.

Animals↗
PubMed1975

Preparation and pharmacological activity of the condensation product of adrenaline with acetaldehyde.

In vitro incubation of adrenaline with acetaldehyde resulted in the formation of an amorphous product (MA 3) which gave origin to two spots on chromatography plates. Preparative TLC allowed us to separate the corresponding substances, MA 4 and MA 5. Gas chromatography-mass spectrometry, ultraviolet and infrared spectra of MA 4 agree with the structure corresponding to 1,2-dimethyl-4,6,7-trihydroxy-1,2,3,4-tetrahydroisoquinoline. MA 5 is very unstable and was not further characterized. Pharmacological experiments were carried out with MA 3 and MA 4 (and in some cases, MA 5) on isolated saphenous vein strips and isolated guinea-pig atria; responses of the nictitating membrane, blood pressure and hind-limb perfusion pressure were obtained in the anaesthetized dog. There were only quantitative differences between the effects of MA 3, MA 4 and MA 5 (where tested). Therefore, these effects are described as effects of TIQs (tetrahydroisoquinolines). TIQs contracted isolated saphenous vein strips, behaving as total agonists; the dose-response curves were displaced to the right by phentolamine and to the left by cocaine (potentiation factor: 2.7 +/- 0.1). In the dog, contractions of the nictitating membrane, rises of blood pressure and of the perfusion pressure (after i.a. injection) were observed. On isolated guinea-pig atria, weak beta adrenergic receptor activation was found. With higher concentrations, beta receptor blockade was observed, for both cardiac and vascular smooth muscle receptors. The effects of TIQs were short-lasting, showing that a rapid inactivation occured both in vitro and in vivo; neuronal uptake appears to play an important role in inactivation, since cocaine was able to block about 70% of the inactivation capacity of isolated vein strips. The effects of nerve stimulation on the vein strips or on the nictitating membrane were reduced by TIQs; however, this did not affect responses to noradrenaline and enhanced those to tyramine or DMPP. Simultaneously with reduction of the effects of electrical stimulation, blockade of inactivation of endogenous and exogenous noradrenaline was induced by TIQs. Marked depletion of noradrenaline levels in the heart, hypothalamus and aorta of the guinea pig was caused by MA 3 (1-3 mg/kg). It is concluded that the condensation products of adrenaline with acetaldehyde are not devoid of pharmacological activity, are taken up by adrenergic nerve terminals and may act as false transmitters. The similarity of effects of TIQs and acetaldehyde suggests that formation of TIQs may occur in vivo, after acetaldehyde (or ethanol) administration, both in the adrenal gland and in sympathetic nerve terminals. These TIQ alkaloids could play an important role in alcoholic intoxication and in the ethanol withdrawal syndrome.

Acetaldehyde↗