cyclic-gmp and Leukemia-P388

The addition of histamine to macrophage-like P388D1 cells resulted in a dose-dependent increase in intracellular calcium [Ca2+]i measured by fura-2 in single cells. The maximum level of [Ca2+]i was obtained by addition of 1 x 10(-4) M histamine. The increase was primarily due to release from the intracellular store. The addition of an H1 specific antagonist pyrilamine before histamine treatment inhibited the increase reversibly, while an H2 specific antagonist cimetidine had no inhibitory effect. Histamine also resulted in a dose-dependent increase in cGMP but not in cAMP. These data suggest the existence of histamine H1 receptors in these cells and histamine may have some biological effect on the function of macrophages via [Ca2+]i and cGMP as the second messengers.

Topics: Animals; Calcium; Cell Line; Cyclic AMP; Cyclic GMP; Fura-2; Histamine; Kinetics; Leukemia P388; Macrophages; Microscopy, Fluorescence; Pyrilamine; Receptors, Histamine H1

The antitumor activity of 5-fluoro-2'-deoxyuridine (FUdR) against P388 leukemia was markedly enhanced by addition of guanosine-5'-monophosphate (GMP). With daily i.p. treatment for 5 d, the combination of FUdR at 100 mg/kg/d and GMP at 300 mg/kg/d showed the highest antitumor effect (more than 290% ILS), while maximum ILS of FUdR alone (100 mg/kg/d) was 94%.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cyclic GMP; Drug Synergism; Floxuridine; Fluorouracil; Leukemia P388; Male; Mice; Mice, Inbred Strains