Stress-up-regulated myocardial endothelin receptors are suppressed by chlo-robenzyltetrahydroberberine CPU86017 and its RS chiral isomer / 中国药科大学学报

Aim: To investigate the changes of endothelin( ET) receptors by isoproterenol in myocardial cells, and the invervention effects of CPU86017 and its RS isomer. Methods: Primary cultures of neonatal rat cardiomyo-cytes were prepared, and isoproterenol was added to each group for modeling, followed by drug interventions with propranolol, CPU86017 and RS chiral isomer respectively. Results: The expressions of ET_A and ET_B were increased by isoproterenol, in which the level of ET_B was higher than ET_A . This phenomenon was adjusted to different degrees by using propranolol, CPU86017 and RS chiral isomer in a dosage-relevant manner. The infervention effect of RS isomer was better than that of CPU86017 at the high dosage( 10 μmol/L). Conclusion: The cardiovascular effects of CPU86017 and RS chiral isomer could be correlative to the inhibition of the over-expressions of ET_A and ET_B.

SM709, Ingredient of Antimelanogenic Bamboo Extract, Blocks Endothelin-1-induced Ca2+i Increase in Human Melanocytes

Endothelins secreted from keratinocytes are intrinsic mitogens and melanogens of human melanocytes in UVB-induced hyperpigmentation. To elucidate the cellular mechanism of antimelanogenic activity of bamboo extract, the effects of three ingredients of bamboo extract on endothelin 1 (ET-1) -induced Ca2+ mobilization were investigated in cultured human melanocytes. ET-1 receptors in human melanocytes were characterized by using specific antagonist, and ET-1 was found to increase intracellular Ca2+ concentration ([Ca2+]i) by activating ET-B receptor. SM709 (1, 2-O-diferulyl-glycerol), an ingredient of bamboo extract, inhibited ET-1-induced [Ca2+]i increase in a concentration- and time-dependent manner, although another ingredients SM707 and SM708 had no effect on ET-1-induced [Ca2+]i increase in human melanocytes. SM709 (100 microM), however, did not affect [Ca2+]i increase induced by thapsigargin and caffeine, suggesting that SM709 has no effect on the Ca2+ store in melanocytes. Furthermore, SM709 did not affect [Ca2+]i increase induced by LPA or ATP, known as G protein-mediated PLC activators like ET-1. Taken together, it is suggested that SM709 antagonizes ET-1-induced transmembrane signaling through ET-B receptor, which maybe a possible underlying mechanism of antimelanogenic activity of bamboo extract in human melanocytes.

Influence of Nitric Oxide Synthesis Inhibition on Endothelin-1 and Its Receptor Expression in Rat Kidney / 대한신장학회잡지

BACKGROUND: The present study was aimed to evaluate the influence of nitric oxide(NO) synthesis inhibition on endothelin(ET) expression in rat kidney. METHODS: Male Sprague-Dawley rats were treated with N(G)-nitro-L-arginine methyl ester(L-NAME, 100 mg/L drinking water) for 4 weeks to inhibit the endogenous synthesis of NO. The tissue expression of ET-1, ET(A) receptor, and ET(B) receptor mRNA in the kidney was determined by reverse transcription-polymerase chain reaction. RESULTS: Tissue levels of NO metabolites were significantly decreased in the plasma and the kidney, along with the increased blood pressure. The expression of ET-1 mRNA was increased in the cortex, but not in the medulla. The expression of ET(A) and ET(B) receptor mRNA was not significantly altered either in the cortex or in the medulla. The plasma level of ET-1 peptide was significantly increased, along with the increased blood pressure, when L-NAME(200 microgram/kg per min, iv) was administered in an acute preparation of animals. Accordingly, the expression of ET-1 mRNA was increased in the cortex, whereas that of ET(A) and ET(B) receptor mRNA was not altered. CONCLUSION: These results suggest that enhanced activity of ET system induced by NO synthesis inhibition may be associated with hypertension although direct association between two factors is not confirmed.

Adrenoceptor and endothelin receptors of artery isolated from colonic cancer / 西安交通大学学报(医学版)

Objective To study the contraction of artery in colonic cancer.Methods Arteries in the cancer part and the cancer ambient part of patients with colonic cancer,the concentration-contractile curves induced by the noradrenaline(NA),sarafotoxin 6c(S6c) and endothelin-1(ET-1) in cumulative application were recorded by myograph.Results The E_(max) and pD_(2)of normal colonic artery contraction induced by NA were(97?19)% and(5.94)?0.17.The E_(max)and pD_(2) of contraction in colonic cancer artery was lower than that in cancer ambient artery(P0.05)).Conclusion The ?-adrenoceptor and ET_(A) receptor are main receptors mediating contraction in colonic cancer artery.