Effects of histamine on the metabolism of isolated rat hepatocytes: roles of H1- and H2-histamine receptors

Abstract

In isolated rat hepatocytes histamine stimulates in a dose-dependent fashion three of the major metabolic pathways: glycogenolysis (70-80% increase over basal), gluconeogenesis from lactate (50-60%), and ureagenesis (50-60%). It was observed that both H1 and H2 receptors mediate the action of histamine and that, in control hepatocytes, the H1-mediated action predominates over the H2. The H1-mediated effect diminished in the absence of extracellular calcium, whereas the H2-mediated action did not. Interestingly, in hepatocytes from hypothyroid rats, the H2 action increased and the H1-mediated effect decreased as compared to those in the controls, with an inversion in efficacy (i.e., H1 greater than H2 in the controls and H2 greater than H1 in cells from hypothyroid rats). Furthermore, it was observed that pertussis toxin treatment and forskolin both enhance the H2-mediated effects without altering the H1-mediated actions of histamine (i.e., H1 approximately equal to H2). The active phorbol ester, phorbol 12-myristate 13-acetate, did not alter the effect of the autacoid. In summary, the data show that histamine modulates liver metabolism through H1 and H2 receptors. The relative importance of the two receptor types in mediating the actions of histamine varies depending on the specific conditions used.