NEURONAL HISTAMINE AND EXPRESSION OF CORTICOTROPIN-RELEASING HORMONE,VASOPRESSIN AND OXYTOCIN IN THE HYPOTHALAMUS - RELATIVE IMPORTANCE OFH-1 AND H-2 RECEPTORS

Centrally administered histamine (HA) stimulates the secretion of the pro-opiomelanocortin-derived peptides ACTH and beta-endorphin as well as prolactin. The effect of IIA on secretion of these adenohypophysial hormones is indirect and may involve activation of hypothalamic neuro ns containing corticotropin-releasing hormone (CRH), arginine-vasopres sin (AVP) or oxytocin (OT). We studied the effect of activating centra l HA receptors by central infusion of HA, HA agonists or antagonists o n expression of CRH, AVP and OT mRNA in the hypothalamic paraventricul ar (PVN) and supraoptic (SON) nuclei. Intracerebroventricular infusion of HA (270 nmol), the H-1-receptor agonist 2-thiazolylethylamine or t he H-2-receptor agonist 4-methylhistamine increased the level of CRH m RNA in the PVN, and OT mRNA in the SON. In contrast, none of these com pounds had any effect on expression of AVP mRNA in the PVN or SON, Adm inistration of the H-1-receptor antagonist mepyramine or the H-2-recep tor antagonist cimetidine had no effect on basal expression of CRH, AV P or OT mRNA in the PVN and/or SON except for a slight inhibitory effe ct of cimetidine on CRH mRNA expression in the PVN. Pretreatment with mepyramine or cimetidine before HA administration inhibited the HA-ind uced increase in OT mRNA levels but had no effect on the HA-induced in crease in CRH mRNA levels in the PVN. We conclude that HA stimulates h ypothalamic CRH and OT neurons by increasing mRNA levels, and this eff ect seems to be mediated via activation of both HA H-1 and H-2 recepto rs.