H-1 AND H-2 HISTAMINE-RECEPTORS IN N-NITROSO-N-METHYLUREA (NMU)-INDUCED CARCINOMAS WITH ATYPICAL COUPLING TO SIGNAL TRANSDUCERS

Two specific binding sites for histamine were characterized in the cell membrane of N-nitroso-N-methylurea (NMU)-induced tumors. The first one, with higher affinity (K-d = 4 +/- 2 nM), was further identified as an H-2 type, while the lower affinity one (35 +/- 10 nM) corresponded to an H-1 receptor. Histamine concentrations up to 50 nM, as well as H-2 agonists, significantly enhanced the phosphoinositide turnover by acting through higher affinity H-2 receptors. On the other hand, histamine at concentrations over 50 nM and H-1 agonists produced a 100% increase in cAMP levels in a response specifically blocked by mepyramine. These H-1 and H-2 histamine receptors that exhibit different linkages to second messenger systems may prove to be a characteristic of cells with a high proliferating capacity, such as undifferentiated or transformed cells.