Intracerebroventricular Injection of Platelet-Activating Factor Induces Secretion of Adrenocorticotropin, Beta-Endorphin and Corticosterone in Conscious Rats: A Possible Link between the Immune and Nervous Systems

Abstract

To investigate whether platelet-activating factor (PAF) exerts an indirect action on immune cells by altering the secretion of hypothalamic-pituitary-adrenal (HPA) axis products, the effects of intracerebroventricular (i.c.v.) PAF on adrenocorticotropic hormone (ACTH), beta-endorphin and corticosterone blood levels were examined in adult male rats. Hormones were radioimmunoassayed on blood samples from conscious or ether-anesthetized rats after i.c.v. injection of PAF or vehicle into the left lateral ventricle. PAF induced significant increases in these stress-related hormones under both, basal and ether-induced stress conditions. The analysis of the time course response to PAF of hormone release into the blood of unrestrained rats revealed that: i.c.v. injection of 5.4 nmol PAF resulted in rapid increases in ACTH and beta-endorphin, at the latest within 15 min after the onset of injection. The maximal response of both hormones was reached within 45 min after the onset of injection and was followed by an elevation of plasma corticosterone. Hormone release is related to the PAF dose infused, the lowest effective PAF concentration was 1 nmol. The stimulatory effect of PAF on ACTH and beta-endorphin secretion was strongly decreased in rats previously treated with purified anti-rat corticotropin-releasing factor (CRF) antibody. These results, associated with the in vitro demonstration that PAF increases CRF release from incubated rat median eminence, strongly support the hypothesis that the stimulatory action of PAF on the secretion of HPA axis products is mediated at least partly, by stimulating hypothalamic CRF release.(ABSTRACT TRUNCATED AT 250 WORDS)