ABSTRACT
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.
Subject(s)
Humans , Adenosine Triphosphate , Caffeine , Endothelin-1 , Endothelins , Hyperpigmentation , Keratinocytes , Melanocytes , Mitogens , ThapsigarginABSTRACT
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.
Subject(s)
Animals , Humans , Male , Rats , Blood Pressure , Drinking , Endothelin-1 , Hypertension , Kidney , NG-Nitroarginine Methyl Ester , Nitric Oxide , Plasma , Rats, Sprague-Dawley , RNA, MessengerABSTRACT
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.