The effects of intracerebroventricular (i.c.v.) injection of histamine and related compounds on plasma adrenocorticotrophic hormone (ACTH) and corticosterone concentrations were studied in conscious rats. 2. Histamine at doses of 5-20 micrograms kg-1 rapidly increased plasma ACTH and corticosterone concentrations almost simultaneously, and subsequent courses were also similar to each other. However, in the case of CRF-41 (i.v.), the plasma ACTH concentration first increased followed by an increase in plasma corticosterone concentration. Even in hypophysectomized rats, a significant increase in plasma corticosterone concentration was induced by histamine at doses of 20 and 50 micrograms kg-1. 3. Histamine at doses of 10 and 20 micrograms kg-1 elicited an increase in the amplitude of adrenal nerve activity, and electrical stimulation to the adrenal nerves resulted in an increase in plasma corticosterone concentration. 4. Both H1-agonist (2-methylhistamine) and H2-agonists (4-methylhistamine and impromidine) also induced similar effects to those of histamine. Pretreatment with pyrilamine caused an inhibition of histamine-induced increase in plasma ACTH and corticosterone concentrations, while both cimetidine and ranitidine failed to inhibit this effect. However, both H2-blockers were effective in inhibiting the 4-methylhistamine-induced elevation of plasma ACTH and corticosterone concentrations. 5. Neither (R)-alpha-methylhistamine nor thioperamide had a significant effect, indicating that the H3-receptor is not involved in the histamine-induced increase in plasma ACTH and corticosterone concentrations. 6. From these findings, it was concluded that (1) electrical signals transmitted from the brain to the adrenal gland through the neurones may be involved in the rapid corticosterone release induced by histamine, and (2) not only H1- but also H2-receptors are implicated in histamine-induced hormone secretions in rats, though the contribution of the H2-receptor is less important than that of the H1-receptor.
