H1 and H2 histamine receptors mediate the production of inositol phosphates but not cAMP in human breast epithelial cells

Objective: In the present work we studied the H-1 and H-2 histamine receptor expression and function in HBL-100 and MCF-10A cells, derived from non-tumorigenic human breast epithelia, and in MCF-10T, the H-ras-transfected MCF-10A counterpart. The signal transduction pathways associated with these receptors, and the expression of proto-oncogenes c-fos, c-myc and c-jun at the mRNA and protein levels, were examined. Results: Saturation analysis using intact cells, showed two binding sites for [H-3]tiotidine and [H-3]mepyramine. Pretreatment of purified membrane with guanosine 5'-gamma thiotriphosphate resulted in the loss of the low affinity component for [H-3]tiotidine binding, and of the high affinity component for [H-3]mepyramine. In both cases, there was no modification in the total number of sites for both ligands. Neither H-1 nor H-2 agonists stimulated cyclic AMP production, though this pathway is functional in these cells. On the other hand, both H-1 and H-2 agonists enhanced phosphoinositide turnover in a dose-dependent fashion, and this induction is pertussis toxin-insensitive. H-1 and H-2 agonists did not influence the expression of c-myc or c-fos mRNA, nor their encoded proteins. Conclusions: These results indicate that the three cell lines examined showed functional H-1 and H-2 histamine receptors, which are involved in the metabolic turnover of inositol phosphates but are ineffective in the modulation of the cyclic AMP response. The fact that H-2 receptors have lost their ability to stimulate cyclic AMP production would imply the loss of a regulatory mechanism of cell growth.