Involvement of β-Adrenergic Receptor Kinase-1 in Homologous Desensitization of Histamine H2 Receptors in Human Gastric Carcinoma Cell Line MKN-45

The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H 2 receptors which are homologously desensitized by histamine. In order to clone the cDNA of a receptor kinase specific for H 2 receptors, we performed RT-PCR at a low annealing temperature using oligo-DNA primers bearing the conserved sequences of the kinase domain of the G protein-coupled receptor kinase (GRK) family. However, we were able to isolate only cDNAs for β-adrenergic receptor kinase 1 (βARK1) and GRK6. Interestingly, treatment of MKN-45 cells with βARK1 antisense phosphorothioate oligo-DNA (PON) resulted in significant loss of desensitization of H 2 receptors by histamine, whereas GRK6 antisense PON had no effect. Thus, βARK1 appears to be involved in the homologous desensitization of H 2 receptors in MKN-45 cells.