Kenzo Kikuchi

Contractile activities of leukotrienes C4 and D4 on vascular strips from rabbits

Abstract Leukotrienes C4 (LTC4) and D4 (LTD4), major components of slow-reacting substances of anaphylaxis (SRS-A), caused dose-dependent contractions of rabbit coronary arteries in concentrations of 10−9 to 10−7 M and 10−10 to 10−7 M, respectively. The potency of LTC4 and LTD4, when compared with the concentration that elicits half of the contraction induced by 25 mM KCl, was 17 and 76 times, respectively, greater than that of histamine. In contrast, other blood vessels from rabbits were either unresponsive (renal artery and vein, mesenteric artery and thoracic aorta) or only weakly responsive (pulmonary artery and vein and portal vein) to both leukotrienes even at 10−7 M. The LTD4-induced coronary contraction was inhibited by FPL 55712 (10−7 and 10−6 M), a selective SRS-A inhibitor, in a dose-dependent manner, but not by diphenhydramine (10−7 M), a histamine H1-receptor blocker or by indomethacin (10−5 M), a prostaglandin synthetase inhibitor, suggesting that LTD4 has a direct effect on the coronary arteries. These results indicate that the leukotrienes may act as potent, selective coronary vasoconstrictors and that SRS-A responsive receptors exist in the rabbit coronary artery.

Stopping of the spontaneous beating of mouse and rat myocardial cells in vitro by a toxin from Vibrio parahaemolyticus

Abstract The effects of a highly purified toxin from Vibrio parahaemolyticus on the beating of cultured mouse and rat myocardial cells and isolated rat atrial preparations were examined. Low concentrations of the toxin stopped the beating of both single isolated myocardial cells and cell clusters obtained in culture from fetal mouse and fetal rat ventricles. These low concentrations depolarized the maximal diastolic potentials and inhibited the generation of action potentials of cultured myocardial cells. The beating activity and the normal generation of action potentials were regained on washing off the toxin or on incubating the cells further in the presence of the toxin. The toxin lost its ability to stop the beating when it was preincubated with the ganglioside, G T1 or G M1 . Spontaneous beating of isolated adult rat atrial preparations stopped in the diastolic phase on addition of the toxin. Before the beating stopped completely, temporary increase in the developed tension and irregular contractions were seen. High concentrations of the toxin caused morphological damage of cultured myocardial cells from fetal mouse and fetal rat ventricles, but did not stop the spontaneous beating, or cause morphological damage of cultured myocardial cells from embryonic chick ventricles.