The effect of adrenaline and Walker-256 tumour-induced cachexia upon Kupffer cell metabolism.
Kupffer cells (KC), the liver macrophages, are able to produce PGE(2), which is involved in immune suppression and in the aggravation of cancer cachexia due to interference with lipid metabolism in the liver. Since tumour-bearing (TB) rats present high plasma epinephrine levels, and this hormone is able to affect macrophage metabolism and function, we have assessed the effect of epinephrine (5 nM) upon Kupffer cell PGE(2) production. Epinephrine induced increased production of PGE(2) both by control (3.5-fold) and TB rats (27 per cent) KC, an effect blocked by propranolol. Enhancement of cAMP content in the cells by addition of isoproterenol (0.1 microM) to the incubations, however, failed to induce the same response in the cells. Nevertheless, when phenylephrine (1 microM) was added to the incubation, a similar pattern of PGE(2) production to that observed for epinephrine was found for control and TB rat KC. We propose that the effect of epinephrine upon KC PGE(2) production is mediated by alpha-adrenergic receptors and that Ca(2+) is involved in the response, since increasing concentrations of the ion added to the incubation medium (0.25, 0.5 and 1.0 mM) enhanced the eicosanoid production, while EDTA abolished the response.
Seelaender
M C
MC
Department of Histology and Embryology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Kazantzis
M
M
Costa Rosa
L F
LF
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002100:Cachexia; D002118:Calcium / Q000378:metabolism; D002279:Carcinoma 256, Walker / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004837:Epinephrine / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D003994:Bucladesine; D000242:Cyclic AMP; D015232:Dinoprostone; D007545:Isoproterenol; D002118:Calcium; D011224:Prazosin; D004837:Epinephrine