Growth hormone releasing factor (GRF) increases free arachidonate levels in the pituitary: a role for lipoxygenase products.
GRF, a specific stimulator of GH release, increased in a concentration- and time-dependent manner pituitary [3H]-arachidonate levels in vitro. This effect was antagonized by 100 nM somatostatin. Exogenous arachidonate also stimulated GH release in vitro. Quinacrine, a phospholipase A2 inhibitor, reduced both basal and GRF-stimulated free arachidonate levels as well as GH release. The cyclooxygenase inhibitor indomethacin was ineffective, while BW755c, which also inhibits the lipoxygenase pathway, produced a further increase in the levels of the fatty acid stimulated by GRF and potently reduced GH release. These results provide additional evidence for the involvement of arachidonate metabolism in the hormone-releasing effect of GRF at the somatotroph.
Canonico
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PL
Speciale
C
C
Sortino
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MA
Cronin
M J
MJ
MacLeod
R M
RM
Scapagnini
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U
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000032:analysis*; D016861:Cyclooxygenase Inhibitors; D004305:Dose-Response Relationship, Drug; D013007:Growth Hormone-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010902:Pituitary Gland / Q000032:analysis / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010446:Peptide Fragments; D011720:Pyrazoles; C036893:somatotropin releasing factor 40; D016718:Arachidonic Acid; D013004:Somatostatin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D013007:Growth Hormone-Releasing Hormone; D008084:Lipoxygenase; D011796:Quinacrine; D007213:Indomethacin