STEROID-SENSITIVITY OF AGONIST BINDING TO PITUITARY CELL-LINE HISTAMINE H-3 RECEPTORS

Histamine H-3 receptors have been identified in rat and guinea-pig pit uitary glands and in the mouse pituitary tumor cell line, AtT-20. Hist amine H-3 receptor agonists are reported to stimulate adrenocorticotro pic hormone (ACTH) release from AtT-20 cells, an effect blocked by his tamine H-3 but not H-1 or H-2 receptor antagonists. To determine wheth er negative feedback regulation of the histamine H-3 receptor-mediated effect might occur, we tested the effects of steroid treatment upon b inding of the agonist [H-3]N-alpha-methylhistamine to AtT-20 cell memb ranes. Consistent with feedback regulation, steroid treatment of the c ells reduced [H-3]N-alpha-methylhistamine binding. The effect was dose -dependent and was greatest for glucocorticoids among the steroids tes ted. As the duration of steroid treatment increased, the amount of [H- 3]N-alpha-methylhistamine binding decreased, to 15% of control at 36 h . However, the effect was not specific for histamine H-3, receptors. S omatostatin inhibits ACTH release from these cells and its binding was similarly reduced by steroid treatment. Because steroids have been re ported to modulate levels of guanine nucleotide-binding proteins, the lack of receptor specificity could reflect an indirect effect of stero ids upon agonist binding and, in fact, we show that [H-3]N-alpha-methy lhistamine binding to these cells, like somatostatin, is pertussis tox in-sensitive. However, steroid treatment does not alter the apparent l evels of pertussis toxin substrate in these cells. Whether steroid tre atment affects histamine H-3 receptors of these cells directly or thro ugh some more subtle effect upon the guanine nucleotide-binding protei ns to which they couple, the result is a negative feedback loop that a ttenuates [H-3]N-alpha-methylhistamine binding to these cells.