Rapid down regulation of pyroglutamyl peptidase II activity by arachidonic acid in primary cultures of adenohypophyseal cells.
Thyrotropin releasing hormone (TRH; pglu-his-proNH2) is inactivated, in the extracellular space, by pyroglutamyl aminopeptidase II (PPII), a narrow specificity ectopeptidase. In adenohypophysis, multiple hormones regulate PPII surface activity. The intracellular pathways of regulation are still poorly understood. Since some of the neurohormones which regulate PPII activity, including TRH and dopamine, transduce in part their effect through modulation of arachidonic acid (AA) mobilization, we have tested its role in regulation of PPII activity in primary cultures of rat adenohypophyseal cells. Melittin concentrations from 0.25 to 1 ug/ml induced a rapid decrease of PPII activity; 0.5 ug/ml caused a maximum effect (38-45% inhibition) at 20-30 min. AA (0.5 or 5 uM) also inhibited PPII activity (42-72%, maximum at 20 min); AA effect was reversible, with values approaching control at 1 h. The inhibitory effect of AA was blocked by lipoxygenase (10 uM nordihidroguaiaretic acid) but not ciclooxygenase inhibitors (10 uM indomethacin) suggesting the involvement of the lipoxygenase pathway. These data show that production of arachidonic acid by adenohypophyseal cells can rapidly but transiently down regulate surface PPII activity. This is the first evidence that AA mobilization can regulate the activity of an ectopeptidase.
Baeza
M A
MA
Departamento de Genetica y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autonoma de Mexico, Morelos.
Ponce
G
G
Joseph-Bravo
P
P
Charli
J L
JL
D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008555:Melitten / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology
D018025:Receptors, Thyrotropin-Releasing Hormone; D008555:Melitten; D016718:Arachidonic Acid; D013973:Thyrotropin-Releasing Hormone; D010741:Phospholipases A; D000626:Aminopeptidases; C023166:pyroglutamyl-peptidase II; D011761:Pyrrolidonecarboxylic Acid