Effect of platelet-activating factor on hypothalamic and hypophyseal pro-opiomelanocortin-related peptides and hypothalamo-pituitary-adrenal axis in the rat.
To examine the effect of platelet-activating factor (PAF-acether) on pro-opiomelanocortin (POMC)-related peptides and on the hypothalamo-pituitary-adrenal axis, we administered PAF-acether and BN 52021, a selective PAF-acether antagonist, to freely moving rats. Minipumps loaded with either PAF-acether (30 micrograms/kg) or the vehicle alone were connected to the jugular vein for 7 days and positioned under the back skin of rats. A group of animals treated with PAF-acether also received 15 mg/kg of BN 52021 orally twice a day. In vivo treatment with PAF-acether alone or in association with BN 52021 did not affect the hypothalamic concentrations of corticotropin-releasing factor (CRF), alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. Using a perifusion system for rat hypothalamic slices, we did not observe any effect of PAF-acether on spontaneous or potassium-induced release of alpha-MSH in vitro. In addition, treatment of rats with PAF-acether alone or in association with BN 52021 did not modify the alpha-MSH or beta-endorphin concentration in the neurointermediate lobe of the pituitary. In contrast, in vivo administration of PAF-acether caused a significant reduction of ACTH concentration in the anterior lobe of the pituitary and a marked decrease in the corticosterone level in plasma and adrenal glands. The inhibitory effect of PAF-acether was reversed by concomitant administration of BN 52021. The ineffectiveness of PAF-acether to modulate in vitro ACTH release from perifused anterior pituitary fragments ruled out a direct effect of PAF-acether on corticotrophs. These findings support the view that PAF-acether exerts a specific inhibitory effect on the hypothalamo-pituitary-adrenal axis.
Blasquez
C
C
URA CNRS 650, Unité Affiliée à l'INSERM, Université de Rouen, Mont-Saint-Aignan, France.
Jégou
S
S
Delarue
C
C
Delbende
C
C
Bunel
D T
DT
Braquet
P
P
Vaudry
H
H
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D004224:Diterpenes; D046934:Ginkgolides; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D000521:alpha-MSH / Q000378:metabolism; D001615:beta-Endorphin / Q000378:metabolism
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010455:Peptides; D010972:Platelet Activating Factor; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; C045856:ginkgolide B