Role of arachidonic acid or its metabolites in growth-hormone-releasing factor-induced release of somatostatin from the median eminence.
The possible involvement of arachidonic acid (AA) release in growth-hormone-releasing factor (GRF)-induced somatostatin (SRIF) release from the median eminence (ME) of the hypothalamus was evaluated in adult male rats using an in vitro incubation system. The MEs were preincubated with [14C]-AA, then washed and incubated with vehicle or test agents, and the release of SRIF and [14C]-AA into the medium was measured. In the experiments designed only to determine SRIF release, the MEs were first preincubated for 30 min. The medium was then discarded and replaced with fresh buffer or test substances and incubated for 10, 20 and/or 30 min. GRF (10(-10) M) stimulated both AA and SRIF release significantly within 20 min, with maximum release occurring at 30 min. The stimulatory effect of GRF on AA release was coincident with the release of SRIF. A phospholipase A2 inhibitor (10(-6) M, quinacrine) completely abolished the stimulatory effect of GRF on both AA and SRIF release. The release of SRIF induced by GRF was also inhibited by both indomethacin (10(-6) M, a cyclooxygenase inhibitor) and metyrapone (10(-6) M, a cytochrome P-450 inhibitor). On the other hand, nordihydroguaiaretic acid (10(-6) M, a lipoxygenase inhibitor) had no effect on GRF-evoked SRIF release. The data presented here suggest that an important GRF-mediated event leading to SRIF secretion is an elevated release of AA from ME fragments in vitro. In conclusion, our data are suggestive that the stimulatory effect of GRF on SRIF release is due, in part, to the release and subsequent metabolism of AA to one or more metabolites.
Aguila
M C
MC
Department of Physiology, University of Texas Southwestern Medical Center, Dallas.
Milenkovic
L
L
McCann
S M
SM
Snyder
G D
GD
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D008797:Metyrapone / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D013004:Somatostatin; D009637:Masoprocol; D013007:Growth Hormone-Releasing Hormone; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D007213:Indomethacin; D008797:Metyrapone