Our findings clearly show that famotidine, classically classified as antagonist or inverse agonists based on cAMP modulation may induce ERK1/2 phosphorylation not only in overexpression models, but also in human gastric adenocarcinoma cells that endogenously express H2R, with potential functional consequences since they are able to modulate the expression of the enzyme responsible for histamine synthesis. Here, MAPK3 is linked to gastric adenocarcinoma.