Abstract
We recently reported the cross-regulation of signaling between platelet-activating factor (PAF)- and ACTH-mediated steroidogenesis. PAF and ACTH act mainly through those receptors accompanied by the activation of protein kinase (PK) C and PKA, respectively. In the present study, since the cortisol (F) synthesis in adrenal fasciculate cells is in part via a calcium/calmodulin-dependent process, we studied the cross-regulation of F secretion among PAF, ACTH, and calcium ionophore A23187 in perfused guinea pig adrenal gland. 1) The infusion of 10 μM A23187 for 5 min significantly stimulated F secretion. The secretory response of F to repeated infusion of A23187 was not reproducible and second infusion only slightly increased F secretion. 2) To confirm PAF and A23187 cross-regulation, 10 nM PAF was perfused for 45-50 min before 10 μM A23187 and vise versa. PAF after perfusion with A23187 resulted in potent suppression. By contrast, the cortisol response to A23187 after PAF was unaffected. 3) To confirm ACTH and A23187 cross-regulation, 100 pg/ml ACTH was perfused for 50-55 min before 10 μM A23187 and vise versa. The cortisol response to ACTH after A23187 was unaffected. Similarly, the cortisol response to A23187 after ACTH was slightly suppressed. These results implicate that cross-regulation among processes activated by PAF receptor-PKC, ACTH receptor-PKA, and calcium/calmodulin might function in the multifactorial regulation of adrenal steroidogenesis. [J Physiol Sci. 2008;58 Suppl:S136]
