Histamine H2 receptor activity during the differentiation of the human monocytic‐like cell line U‐937

Abstract

Histamine H₂ receptor activity (cAMP generation) has been characterized in U‐937 cells before and after retinoic acid‐induced differentiation into monocyte‐/macrophage‐like cells. The differentiation is associated with a decreased capacity of U‐937 monocytes to generate cAMP under basal conditions or after cell surface receptor stimulation by histamine, isoproterenol and PGE₁. In contrast, the potencies of the hormones are unchanged during monocytic maturation (EC ₅₀ values = 3.2–4.6 × 10⁻⁶ M histamine, 4.6–7 × 10⁻⁹ M isoproterenol, 2–4.6 × 10⁻⁶ M PGE₁). The data support the view that histamine and cAMP‐inducing agents may control the proliferation and differentiation of normal and leukemic cells committed to monocytic maturation in man. They also raise the possibility that normal human monocytes also possess functional H₂ receptors and that histamine may be implicated in the regulation of monocyte/macrophage functions.