Abstract
Platelet-activating factor (PAF) is a highly potent stimulator of the secretion of glucocorticoids. PAF acts mainly through PAF receptor accompanied by the activation of protein kinase (PK) C. While, ACTH and cholera toxin (CTX) acts through the activation of PKA. In the present study, we studied the cross-regulation of cortisol (F) secretion among PAF, ACTH, and CTX by perfused guinea pig adrenal gland. 1) The infusion of 1nM PAF or 10pg/ml ACTH for 5 min significantly stimulated F secretion. Concurrent application of PAF and ACTH evoked F secretion less than additional. The F response to repeated infusion of this mixture was reproducible. 2) The infusion of 20-2000 ng/ml CTX for 5 min dose-dependently augmented F secretion. The peak of F secretion to 20 ng/ml CTX reached a plateau about 40 to 60 min after start of infusion that persisted thereafter. The application of 10 nM PAF from 95 to 100 min after the infusion of CTX induced additional augmentation of F secretion above CTX-induced cortisol output. The application of 100 pg/ml ACTH had no effect. 3) When applied 10 nM PAF repeatedly from 95 to 100 min and from 140 to 145 min after the infusion of CTX, the completely same amounts of F were secreted above CTX-induced cortisol output. When applied 10 nM PAF 45 min before and 85 min after the infusion of CTX, almost same amounts of cortisol were secreted above basal and CTX-induced cortisol secretion.These results implicate that PAF not only induces cortisol secretion but also markedly augments Gs-activated cortisol secretion. [J Physiol Sci. 2007;57 Suppl:S75]