The naturally occurring mutation Y197C does not affect the expression or signaling of the human histamine H receptor.

There is evidence for genetic polymorphism within the human histamine H receptor (hHR), and a Tyr to Cys exchange at position 197 (Y197C), located in the amino terminus of the fifth transmembrane domain, has been reported. In this work we compared the expression and the pharmacological and signaling properties of wild-type (hHR) and mutant (hHR) receptors transiently expressed in CHO-K1 cells. The hHR cDNA was created by overlap extension PCR amplification. Receptor expression and affinity were assessed by N-α-[methyl-H]-histamine binding to cell membranes and intact cells. Receptor function was evaluated by stimulation of [S]-GTPγS binding to cell membranes and by inhibition of forskolin-induced cAMP accumulation in intact cells. The hHR and hHR were expressed at similar levels (761±68 and 663±66fmol/mg protein for membranes, and 13,434±1533 and 15,894±1884 receptors per cell, respectively). There were no significant differences in the affinities for HR agonists or antagonists/inverse agonists between the hHR and hHR, and the HR agonist RAMH was similarly efficacious and potent to stimulate [S]-GTPγS binding and to inhibit forskolin-induced cAMP accumulation. These results indicate that the Y197C mutation does not affect the expression, ligand affinity or signaling of the human H receptor.