The Alkyl-Ether Phospholipid Platelet-Activating Factor is a Stimulator of the Hypothalamic-Pituitary-Adrenal Axis in the Rat*

Platelet-activating factor (PAF) is a naturally occurring alkyl-ether phospholipid which serves as an extracellular mediator in various cellular processes. Here we examined the effects of PAF on the activity of the hypothalamic-pituitary-adrenal axis in vivo and in vitro. PAF injected iv to rats (125, 250, and 500 ng/100 g BW) caused significant stimulation of pituitary ACTH and adrenal corticosterone secretion. The peak of PAF effect was recorded 10 min after the injection. Intraperitoneal injection of the PAF receptor antagonist BN 52021 prevented the ACTH-releasing effect of PAF. In explanted rat hypothalami maintained viable in vitro, PAF stimulated immunoreactive CRH secretion in a bell-shaped dose-response fashion. The maximal stimulatory effect occurred at the concentration of 10 nM. Higher concentrations appeared to cause desensitization. Alprazolam (1 microM) and BN 52021 (1 microM), two structurally different PAF receptor antagonists, inhibited this effect. The inhibitors of arachidonic acid metabolism, indomethacin, eicosatetraynoic acid, and the calcium channel blocker verapamil, inhibited PAF-stimulated CRH secretion, suggesting mediation by Ca2+ influx and phospholipase-A2 activation. In addition, we found that 1 nM PAF weakly stimulated ACTH secretion by dispersed rat pituicytes. This stimulatory effect of PAF was also inhibited by the receptor antagonists alprazolam and BN 52021. Our data suggest that PAF plays a role in the activation of the hypothalamic-pituitary-adrenal axis and glucocorticoid secretion and can perhaps serve as a mediator in the interactions of the immune system with the central nervous system.