EMODIN PHARMACOKINETICS IN RABBITS

CMUR > College of Pharmacy > School of Pharmacy/Master Degree Program, Ph. D program > Journal articles > Item 310903500/31035

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Title:	EMODIN PHARMACOKINETICS IN RABBITS
Authors:	LIANG, JW;HSIU, SL;WU, PP;CHAO, PDL
Contributors:	藥學院藥學系;CHINA MED COLL,SCH PHARM,TAICHUNG,TAIWAN;CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG,TAIWAN
Date:	1995
Issue Date:	2010-09-24 18:54:50 (UTC+8)
Publisher:	GEORG THIEME VERLAG
Abstract:	1 Our previous study demonstrated that YC-1, a derivative of benzylindazole, is a novel activator of soluble guanylate cyclase (sGC) in rabbit platelets. This work investigated whether the antiplatelet effect of YC-1 was mediated by a nitric oxide (NO)/sGC/cyclic GMP pathway in human platelets. 2 In human washed platelets, YC-1 inhibited platelet aggregation and ATP released induced by U46619 (2 mu M), collagen (10 mu g ml(-1)) and thrombin (0.1 u ml(-1)) in a concentration-dependent manner with IC50 values of (mu M) 2.1 +/- 0.3, 11.7 +/- 2.1 and 59.3 +/- 7.1, respectively. 3 In a 30,000 g supernatant fraction from human platelet homogenate, YC-1 (5-100 mu M) increased sGC activity in a concentration-dependent manner. At the same concentration-range, YC-1 elevated cyclic GMP levels markedly, but only slightly elevated cyclic AMP levels in the intact platelets. 4 MY-5445, a selective inhibitor of cyclic GMP phosphodiesterase, potentiated the increases in cyclic GMP caused by YC-1, and shifted the concentration-anti-aggregation curve of YC-1 to the left. In contrast, HL-725, a selective inhibitor of cyclic AMP phosphodiesterase, did not affect either the increases in cyclic nucleotides or the anti-aggregatory effect caused by YC-1. 5 Methylene blue, an inhibitor of sGC, blocked the increases of cyclic GMP caused by YC-1, and attenuated markedly the anti-aggregatory effect of YC-1. The adenylate cyclase inhibitor, 2',5'-dideoxyadenosine (DDA) did not affect YC-1-induced inhibition of platelet aggregation. 6 Haemoglobin, which binds NO, prevented the activation of sGC and anti-aggregatory effect caused by sodium nitroprusside, but did not affect YC-1 responses. 7 These results would suggest that YC-1 activates sGC of human platelets by a NO-independent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway.
Relation:	PLANTA MEDICA 61(5):406-408
Appears in Collections:	[School of Pharmacy/Master Degree Program, Ph. D program] Journal articles

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