Hormetic acute response and chronic effect of ethanol on adenine nucleotide hydrolysis in rat platelets.
The objective of this study was to verify the acute and chronic effects of ethanol on platelet NTPDase and 5'-nucleotidase activities. These enzymes modulate platelet function by regulating adenine nucleotide bioavailability and adenosine production. In the acute treatment, doses of 0.8, 2.0, 4.0, 6.0 and 8.0 g/kg ethanol were administered via orogastric tube, and induced a biphasic or hormetic effect on ATP, ADP and AMP platelet hydrolysis. Ethanol at a dose of 0.8 and 2.0 g/kg increased NTPDase activity (44 and 35%, P < 0.0001) with ATP as substrate, whereas when ADP was used there was only a tendency for NTPDase activity to increase. ATP and ADP hydrolysis decreased by 31-77% (P < 0.0001) in 4.0, 6.0 and 8.0 g/kg of ethanol compared to the control. AMP hydrolysis showed a tendency to increase at ethanol doses of 0.8 and 2.0 g/kg, but was inhibited by 45-100% (P < 0.0001) at the higher doses. Chronic treatment consisted of the oral administration of 20% ethanol solution during 31 weeks as the only source of liquid and inhibited NTPDase activity (15 and 20%, P < 0.05) with ATP and ADP as substrate, respectively. However, AMP hydrolysis by 5'-nucleotidase increased by 40% (P < 0.05). Thus, we speculate that the effects of ethanol on NTPDase and 5'-nucleotidase activities could be related with the platelets alterations commonly observed in alcohol users.
Dias
Glaecir R Mundstock
GR
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS 97105-900, Brazil.
Schetinger
Maria Rosa Chitolina
MR
Spanevello
Roselia
R
Mazzanti
Cinthia Melazzo
CM
Schmatz
Roberta
R
Loro
Vânia Lúcia
VL
Morsch
Vera Maria
VM
D015720:5'-Nucleotidase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
D000227:Adenine Nucleotides; D000431:Ethanol; D015720:5'-Nucleotidase