Interactions between histamine H1 receptor and its antagonists by using cell membrane chromatography method

OBJECTIVES: A high histamine H1 receptor (H1 R) expression cell membrane chromatography (CMC) method was developed to investigate the affinity of ligands for H1 R. METHODS: The affinity of ligands for H1 R was evaluated by frontal analysis. Competition studies and molecular docking study were utilized to study the interactions that occurred at specific binding sites on H1 R. KEY FINDINGS: The KD values measured by frontal analysis were (8.72 ± 0.21) × 10(-7) M for azelastine, (9.12 ± 0.26) × 10(-7) M for cyproheptadine, (9.90 ± 0.18) × 10(-7) M for doxepin, (1.42 ± 0.13) × 10(-6) M for astemizole, (2.25 ± 0.36) × 10(-6) M for chlorpheniramine and (3.10 ± 0.27) × 10(-6) M for diphenhydramine. The results had a positive correlation with those from radioligand binding assay. The ability of displacement order measured on the binding sites occupied by doxepin was doxepin (KD , (2.95 ± 0.21) × 10(-8) M) > astemizole (KD , (5.03 ± 0.18) × 10(-7) M) > chlorpheniramine (KD , (1.27 ± 0.16) × 10(-6) M) > cyproheptadine (KD , (1.61 ± 0.27) × 10(-6) M), whose order met with the scores by molecular docking study. CONCLUSIONS: The studies showed CMC could be applied to investigate drug-receptor interactions.