Gangliosides prevent the dimethyl sulphoxide-induced increases in [3H]-noradrenaline release from rat isolated atria.
1. In the rat isolated atria labelled with [3H]-noradrenaline ([3H]-NA), the exposure to 1-4% v/v dimethyl sulphoxide (DMSO) during 15 min caused a concentration-dependent increase in the spontaneous outflow of tritiated products, which reached up to 50% with 2% DMSO and up to 100% with 4% DMSO. These effects were entirely prevented by a 2 h in vitro pretreatment with 50 microM bovine brain gangliosides mixture (BBG). 2. The pattern of the spontaneous release of tritiated products was 17.5 +/- 1.9% of [3H]-NA; 38.7 +/- 2.1% of [3H]-3,4-dihydroxyphenylglycol ([3H]-DOPEG); 36.1 +/- 2.4% of [3H]-O-methylated deaminated metabolites ([3H]-OMDA); 4.7 +/- 0.9% of [3H]-3,4-dihydroxymandelic acid ([3H]-DOMA) and 2.9 +/- 0.2% of [3H]-NMN. After 10 min exposure to 2% DMSO, the increase in basal outflow by this agent consisted of 7.4 +/- 2.5% [3H]-NA and 89.0 +/- 3.6% [3H]-DOPEG. The 2 h preincubation with 50 microM BBG protected from the increase of total radioactivity and also from the metabolic alterations caused by DMSO. The BBG per se did not modify either the basal efflux or the metabolic fate of the [3H]-transmitter. 3. In addition to enhancing the spontaneous outflow of radioactivity, the exposure to 2% v/v DMSO increased by 400% the overflow of the [3H]-transmitter elicited by nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Lorenzo
P S
PS
Instituto de Investigaciones Farmacológicas, CONICET, Buenos Aires, Argentina.
Adler-Graschinsky
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D005732:Gangliosides / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005732:Gangliosides; D015102:3,4-Dihydroxyphenylacetic Acid; D009638:Norepinephrine; D004121:Dimethyl Sulfoxide