Alpha 1-adrenergic stimulation of arachidonic acid release and metabolism in a rat thyroid cell line. Mediation of cell replication by prostaglandin E2.
The rat thyroid cell line, FRTL-5, expresses an alpha 1-adrenergic receptor when exposed to thyrotropin. We have found that occupation of this alpha 1-adrenergic receptor by norepinephrine stimulated the release of [3H]arachidonic acid from prelabeled cells. Arachidonic acid was metabolized primarily to prostaglandin E2 and to much smaller amounts of 11-hydroxy-5,8,11,13-eicosatetraenoic acid, 15-hydroxy-5,8,11,13-eicosatetraenoic acid, prostaglandin D2, and thromboxane B2. Synthesis of all these metabolites was inhibited by the cyclooxygenase inhibitor indomethacin. When FRTL-5 cells were starved of thyrotropin for 24 h, norepinephrine nearly doubled [3H]thymidine uptake into DNA. Cyclooxygenase inhibitors inhibited norepinephrine-stimulated thymidine uptake by 60-70%. Of several arachidonic acid metabolites tested, none was able to stimulate thymidine uptake directly in the presence of indomethacin. Prostaglandin E2, however, was able to restore [3H]thymidine uptake when added together with norepinephrine in the presence of indomethacin. Thus, occupation of an alpha 1-adrenergic receptor in a functional rat thyroid cell line leads to arachidonic acid release. Subsequent metabolism of the arachidonic acid by the cyclooxygenase pathway leads to synthesis of prostaglandin E2, which mediates a norepinephrine-stimulated activity related to cell replication.
Burch
R M
RM
Luini
A
A
Mais
D E
DE
Corda
D
D
Vanderhoek
J Y
JY
Kohn
L D
LD
Axelrod
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D013972:Thyrotropin; D000242:Cyclic AMP; D015232:Dinoprostone; D013936:Thymidine; D009638:Norepinephrine; D007213:Indomethacin