Antagonism between the metabolic responses induced by epinephrine and piroxicam on isolated rat hepatocytes.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most employed therapeutic agents. They have a wide spectrum of biological effects, some of which are independent of cyclooxygenase inhibition, such as the alterations on the components of signal transduction systems. In particular, previous data from our laboratory suggested an antagonism between epinephrine and piroxicam, one of the most prescribed NSAIDs. Thus, this study deals with the epinephrine-piroxicam antagonism recorded for metabolic responses in isolated rat hepatocytes. The obtained results show that epinephrine stimulates lactate and ethanol consumption, stimulates glucose release from lactate only, and has no effect on cellular triacylglycerides content. Otherwise, in a dose-dependent basis, piroxicam stimulates lactate and ethanol consumption accompanied by an increase in triacylglycerides content, without changes in glucose release by hepatocytes. Piroxicam blocks the epinephrine-induced stimulation of glucose release from lactate, and epinephrine blocks the piroxicam-mediated increase in triacylglycerides content from lactate or ethanol. In contrast, the effects of epinephrine and piroxicam, promoting the consumption of lactate and ethanol, are not antagonized or added after the simultaneous administration of both compounds. This last result is probably related to the ability of both compounds to stimulate oxygen consumption. On isolated rat liver mitochondria, micromolar doses of piroxicam partially uncouple oxidative phosphorylation, and paradoxically stimulates an ATP-dependent mitochondrial function as citrullinogenesis. These results show for first time, on isolated rat hepatocytes, an antagonism between the metabolic responses of epinephrine and piroxicam, at the concentration found in plasma after its therapeutical administration.
Riveros-Rosas
H
H
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF. hriveros@servidor.unam.mx
Zentella de Piña
M
M
Guinzberg
R
R
Saldaña-Balmori
Y
Y
Julián-Sánchez
A
A
Saavedra-Molina
A
A
Piña
E
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004837:Epinephrine / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010894:Piroxicam / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014280:Triglycerides; D010894:Piroxicam; D019344:Lactic Acid; D000431:Ethanol; D000244:Adenosine Diphosphate; D005947:Glucose; D004837:Epinephrine