Steroid-sensitivity of agonist binding to pituitary cell line histamine H3 receptors.
Histamine H3 receptors have been identified in rat and guinea-pig pituitary glands and in the mouse pituitary tumor cell line, AtT-20. Histamine H3 receptor agonists are reported to stimulate adrenocorticotropic hormone (ACTH) release from AtT-20 cells, an effect blocked by histamine H3 but not H1 or H2 receptor antagonists. To determine whether negative feedback regulation of the histamine H3 receptor-mediated effect might occur, we tested the effects of steroid treatment upon binding of the agonist [3H]N alpha-methylhistamine to AtT-20 cell membranes. Consistent with feedback regulation, steroid treatment of the cells reduced [3H]N alpha-methylhistamine binding. The effect was dose-dependent and was greatest for glucocorticoids among the steroids tested. As the duration of steroid treatment increased, the amount of [3H]N alpha-methylhistamine binding decreased, to 15% of control at 36 h. However, the effect was not specific for histamine H3 receptors. Somatostatin inhibits ACTH release from these cells and its binding was similarly reduced by steroid treatment. Because steroids have been reported to modulate levels of guanine nucleotide-binding proteins, the lack of receptor specificity could reflect an indirect effect of steroids upon agonist binding and, in fact, we show that [3H]N alpha-methylhistamine binding to these cells, like somatostatin, is pertussis toxin-sensitive. However, steroid treatment does not alter the apparent levels of pertussis toxin substrate in these cells. Whether steroid treatment affects histamine H3 receptors of these cells directly or through some more subtle effect upon the guanine nucleotide-binding proteins to which they couple, the result is a negative feedback loop that attenuates [3H]N alpha-methylhistamine binding to these cells.
West
R E
RE
Schering-Plough Research Institute, Kenilworth, NJ.
Myers
J
J
Zweig
A
A
Siegel
M I
MI
Egan
R W
RW
Clark
M A
MA
D000244:Adenosine Diphosphate / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000378:metabolism* / Q000494:pharmacology; D008761:Methylhistamines / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017442:Histamine Agonists; D008761:Methylhistamines; D018100:Receptors, Histamine H3; D013256:Steroids; D010566:Virulence Factors, Bordetella; D000244:Adenosine Diphosphate; C069357:alpha-methylhistamine; D000324:Adrenocorticotropic Hormone; D001623:Betamethasone; D037342:Pertussis Toxin