HIGH-AFFINITY HISTAMINE H3-RECEPTORS REGULATE ACTH RELEASE BY ATT-20 CELLS

The distribution of high affinity histamine H-3 receptors in various tissues from guinea pig has been determined using [H-3]N(alpha)-methylhistamine binding. In the course of those studies, it was observed that the pituitary gland contains H-3 receptors. Using this radioligand, we have now identified and characterized H-3 receptors on the AtT-20 cell line from a murine anterior pituitary tumor. This line has approximately 5000 high affinity (K(D)) = 0.7 nM) H-3 binding sites per cell. Competition binding with standard H-1, H-2 and H-3 agents has confirmed that these sites are, indeed, H-3 receptors. The H-3 receptor specific agonist, (R)-alpha-methylhistamine increased the release of adrenocorticotropic hormone (ACTH) from AtT-20 cells in a dose- and time-dependent manner, while histamine and the H-2 agonist dimaprit were significantly less potent. Furthermore, this response was blocked by thioperamide, an H-3 receptor specific antagonist. but not by the H-1 and H-3 antagonists, chlorpeniramine and cimetidine. These results identify for the first time, a cell line expressing H-3 receptors and indicate that the high affinity histamine H-3 receptor regulates ACTH release from that cell.