HISTAMINE H1 RECEPTOR OCCUPANCY TRIGGERS INOSITOL PHOSPHATES AND INTRACELLULAR CALCIUM MOBILIZATION IN HUMAN NONPIGMENTED CILIARY EPITHELIAL-CELLS

Agonists and antagonists of histamine were used to characterize the stimulation of inositol phosphates formation and elevation of intracellular Ca2+ by histamine in cultured non-pigmented epithelial (NPE) cells from human ciliary body. Agonists specific for the H-1 histamine receptor subtype were 20- to 200-fold more potent than the H-2-specific agonists tested, and 5-16% as potent as histamine in inositol phosphates stimulation. An H-1 antagonist was 10,000-fold more potent than an H-2 antagonist in blocking histamine stimulation of inositol phosphates. H-1 agonists also mimicked and H-1 antagonists inhibited the elevation of intracellular Ca2+ by histamine. The first phase of the Ca2+ response to histamine was largely independent of extracellular Ca2+ while the second phase required extracellular Ca2+. Dose-response curves for histamine elevation of intracellular Ca2+ (EC50 = 10-mu-M, maximum at 100-mu-M)and inositol phosphates (EC50 = 2-mu-M, maximum at 100-mu-M) were similar. These data support the characterization of the NPE histamine receptor as an H-1 receptor linked to elevation of inositol phosphates and intracellular Ca2+.