Modulation of norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes by n-3 fatty acids.
This work showed that docosahexaenoic (22:6n-3) and eicosapentaenoic (20:5n-3) acid supplementation for 48 h have opposite effects on the norepinephrine-stimulated cyclic AMP accumulation in rat pinealocytes. We found that 22:6n-3 supplementation of pineal cells, done by increasing specifically 22:6n-3 in phospholipid and triacylglycerol pools, led to inhibition of norepinephrine-stimulated cyclic AMP production whereas 20:5n-3 supplementation, by increasing 20:5n-3, and 22:5n-3 and 22:6n-3 in the same pools, stimulated it. In contrast, direct treatment of pinealocytes with each fatty acid (50 microM) did not affect cyclic AMP production in the presence of (0.1-10 microM) norepinephrine. The results indicate that, using pharmacological agents such as forskolin or prazosin: (a) neither basal nor forskolin-stimulated cyclic AMP levels were modified in fatty acid-supplemented cells compared to control cells; (b) in the presence of 1 microM prazosin, the activation by 20:5n-3 was still effective whereas no additional inhibition of norepinephrine stimulation was observed in 22:6n-3-supplemented cells. Taken together our results suggest that 22:6n-3 or 20:5n-3 supplementation modulates specifically the alpha 1- or beta-adrenoceptors in the rat pineal gland.
INSERM U352, Laboratoire de Biochimie et Pharmacologie, INSA Lyon, Villeurbanne, France.
I
I
Delton-Vandenbroucke
N
N
Sarda
P
P
Molière
M
M
Lagarde
A
A
Gharib
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004357:Drug Synergism; D005227:Fatty Acids / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D005227:Fatty Acids; D010743:Phospholipids; D014280:Triglycerides; D005576:Colforsin; D000242:Cyclic AMP; D009638:Norepinephrine; D011224:Prazosin