Studies on the involvement of histamine in the hypothalamic-pituitary-adrenal axis activation induced by nerve growth factor

Nerve growth factor (NGF) has been shown to stimulate the hypothalamic-pitu itary-adrenocortical (HPA) axis. Since NGF induces the release of histamine from mast cells and in consideration of the fact that histamine is an HPA axis activator, we investigated whether NGF adrenocortical stimulation is m ediated by histamine. To accomplish with it, the H-1 histamine antagonist p romethazine and the H-2 antagonists metiamide and zolantidine were used in freely-moving cannulated rats, The increase in plasma corticosterone concen tration induced by histamine administration was prevented completely by pro methazine pretreatment but was unaffected by the H-2 antagonists. Neither H -1 nor H-2 antagonists affected the adrenocortical stimulation induced by N GF administration. Moreover, since mast cells are reportedly present in the rat adrenal gland and the locally released histamine mediates the release of adrenaline which, in turn, stimulates glucocorticoid synthesis and secre tion, we studied the effect of NGF on basal and ACTH-stimulated corticoster one release from in vitro isolated quartered adrenal glands and collagenase -dispersed adrenal cells. The results from these in vitro experiments have indicated that NGF modified neither spontaneous nor stimulated corticostero ne release. Altogether these observations suggest that: endogenous histamin e is unlikely to be involved in HPA axis stimulation by NGF and reinforce t he previously proposed concept of an active participation of NGF in the con trol of adrenocortical activity. (C) 2000 Elsevier Science Inc. All rights reserved.