Effect of PAF receptor antagonists on adrenocortical secretion induced by ACTH in normal and athymic nude mice.
The effect of SM12502 and CV6209, platelet-activating factor (PAF) receptor antagonists on corticosterone (B) secretion induced by ACTH was examined in the perfused adrenals of CD1 ICR (normal) and CD1 ICR nu/nu (athymic) mice. Bilateral adrenals were perfused in situ with an artificial medium equilibrated by 95% O2 + 5% CO2. Continuous infusion of 10 microM SM12502 or CV6209 inhibited the B response to 100 pg/ml ACTH markedly in normal mice but insignificantly in athymic mice. Infusion of PAF did not significantly affect B secretion in either normal or athymic mice. Administration of 0.1 microM of N-methylcarbamyl PAF, a nonmetabolizable PAF agonist, significantly increased B secretion in normal mice, but not in athymic mice. Infusion of SM12502 significantly depressed the B response to 10 microM forskolin or 1 mM dibutyryl cyclicAMP (cAMP) in normal mice, but not in athymic mice. The results indicate that endogenous PAF and its receptor may play a role in the ACTH-initiated signaling pathway at the phase after responsiveness to cAMP and its receptor may have little function in athymic mice.
Han
L
L
Department of Physiology and Orthopedic Surgery, Nagasaki University School of Medicine, Japan.
Yang
H
H
Shimada
T
T
Hirose
T
T
Koyanagi
M
M
Matsumoto
I
I
Iwasaki
K
K
Aikawa
T
T
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013844:Thiazoles; D053778:Thiazolidines; C039351:platelet activating factor receptor; C053321:CV 6209; C065776:3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one; D005576:Colforsin; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone