title: Platelet-activating factor acts on cortisol secretion by perfused guinea-pig adrenals via calcium-/phospholipid-dependent mechanisms.
abstract: Bilateral adrenals of the guinea pig were perfused in situ with an artificial medium equilibrated with 95% O2/5% CO2. Platelet-activating factor (PAF) induced biphasic cortisol responses, which reached a maximum at 10 nM PAF and declined at 100 nM. The effect of the PAF receptor antagonists CV-3988 and CV-6209 on PAF-stimulated cortisol secretion was examined. Prior exposure of adrenal glands to 10 microM CV-3988 or a simultaneous incubation with 10 microM CV-6209 abolished the cortisol response to 10 nM PAF. Lyso-PAF (a PAF precursor and breakdown product) did not affect cortisol secretion. Concentrations of 5-12.5 microM 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a protein kinase C (PKC) inhibitor, abolished subsequent cortisol secretion in response to 10 nM PAF. N-[2-(Methylamino)ethyl]-5-isoquinoline sulfonamide dihydrochloride (H-8), a protein kinase A inhibitor, was less effective. A calcium ionophore (A23187) at 3.3 and 10 microM increased cortisol secretion, but the activator of PKC, l-alpha-1-oleoyl-2-acetyl-sn-3-glycerol (OAG), at 50 microM had no effect. When infused simultaneously, OAG (50 microM) and A23187 (3.3 microM) stimulated cortisol secretion synergistically. The secretory response of cortisol to repeated infusions of adrenocorticotrophin (100 pg/ml) or forskolin (10 microM) was essentially reproducible. By contrast, cortisol secretion in response to repeated infusions of PAF (10 nM) or OAG plus A23187 was not reproducible and the second response was diminished compared with the first. Our findings suggest that PAF plays a role in the regulation of steroidogenesis via a mechanism mediated by the PAF receptor and PKC.
authors.affiliation: Department of Physiology, Nagasaki University School of Medicine, Nagasaki 852-8523, Japan. tshimada@net.nagasaki-u.ac.jp
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimada
authors.forename: Taeko
authors.initials: T
authors.lastname: Hirose
authors.forename: Itsuro
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Aikawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000378:metabolism*; D007476:Ionophores / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010477:Perfusion; D010742:Phospholipid Ethers / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D004075:Diglycerides; D007476:Ionophores; D007546:Isoquinolines; D010742:Phospholipid Ethers; D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C053321:CV 6209; D005576:Colforsin; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; C037913:CV 3988; D000324:Adrenocorticotropic Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium; D003345:Corticosterone; D006854:Hydrocortisone