Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion

Prostaglandins and histamine in the hypothalamus are involved in the regulation of oxytocin and vasopressin secretion, and appear to be involved in the mediation of pituitary hormone responses to immunochallenges. Therefore, we investigated in conscious male rats: (i) whether blockade of H-1 or H-2 receptors affected the oxytocin and vasopressin responses to prostaglandins and (ii) whether blockade of prostaglandin synthesis affected the oxytocin and vasopressin responses to histamine or to Escherichia coli lipopolysaccharide (LPS), in order to determine any interaction between prostaglandins and histamine in the hypothalamus. Oxytocin secretion was dose-dependently stimulated by intracerebroventricular infusion of 1 or 5 mug of PGE(1), PGE(2) or PGF(2alpha), with PGE(2) being the most potent of the compounds used. Prior central infusion of the H-1 receptor antagonist mepyramine or the H-2 receptor antagonist cimetidine significantly inhibited the oxytocin response to all three prostaglandins by approximately 50%. Vasopressin secretion was increased by PGE(1) but not by PGE(2) or PGF(2alpha). The stimulatory effect of PGE(1) was almost annihilated by prior administration of mepyramine or cimetidine. Central infusion of histamine or immunochallenge with LPS administered intraperitoneally increased oxytocin and vasopressin secretion four-and two-fold, respectively. Pretreatment with systemic injection of the prostaglandin synthesis inhibitor indomethacin dose-dependently reduced the oxytocin response and prevented the vasopressin response to histamine or LPS. We conclude that histamine and PGE(1), PGE(2) or PGF(2alpha) interact in the regulation of oxytocin secretion, whereas histamine and only PGE(1) interact in the regulation of vasopressin secretion. Furthermore, histamine as well as LPS may affect oxytocin and vasopressin neurones via activation of prostaglandins, probably in the hypothalamic supraoptic nucleus.