RESPONSES OF ANTERIOR-PITUITARY HORMONES AND HYPOTHALAMIC HISTAMINE TO BLOCKADE OF HISTAMINE SYNTHESIS AND TO SELECTIVE ACTIVATION OR INACTIVATION OF PRESYNAPTIC HISTAMINE H-3 RECEPTORS IN STRESSED RATS

The stress-induced release of anterior pituitary hormones and changes in hypothalamic content of histamine (HA) and its metabolite tele-meth ylHA (t-meHA) were studied in male rats during inhibition of HA synthe sis or activation or blockade of HA H-3 receptors. Pretreatment with t he HA synthesis inhibitor alpha-fluoromethylhistidine (alpha-FMH; 200 mug intracerebroventricularly (icv) at -120 min) or the specific H-3 r eceptor agonist R(alpha)methylhistamine (Rm HA; 10 mg/kg intraperitone ally (ip) at -180 and -60 min) inhibited by 30-80% the responses of pr olactin (PRL), corticotropin (ACTH) and beta-endorphin (beta-END) immu noreactivity to 1, 2.5 or 5 min of restraint stress (p < 0.05-0.01), b ut had no effect on basal secretion of the hormones. The inhibitory ef fect of the H-3 receptor agonist Rm HA (I 0 mg/kg x 2) on the hormone response to 5 min of restraint stress was prevented by simultaneous ip administration of the H-3 receptor antagonist thioperamide. alpha-FMH reduced the hypothalamic content of HA 60% and that of t-meHA 30%, wh ile RmHA had no effect on the HA content. Restraint stress for 5 min d id not affect the HA and t-meHA contents, which may be due to the shor t duration of stress exposure. Pretreatment with the H-3 receptor anta gonist thioperamide (5 or 10 mg/kg ip at -120 min) had no effect on ba sal or restraint stress-induced release of PRL, ACTH or beta-END, alth ough the compound increased the hypothalamic content of t-meHA 2-fold. Insulin-induced (I IU/kg ip) hypoglycemia increased the plasma concen tration of ACTH and beta-END 2- and 1.5-fold, respectively, and increa sed the hypothalamic content of t-meHA almost 2-fold, which indicates an increased turnover of neuronal HA. Alpha-FMH or RmHA prevented the insulin-induced release of ACTH and beta-END. Insulin had no significa nt effect on PRL secretion. In conclusion, the findings that the respo nse of PRL, ACTH and alpha-END to stress or insulin-induced hypoglycem ia was inhibited by blockade of HA synthesis or activation of H-3 rece ptors and that hypothalamic HA turnover increased in response to hypog lycemia further implicate a role of hypothalamic histaminergic neurons in the neuroendocrine regulation of pituitary hormone secretion.