抗血栓形成的烟酰胺增加人血小板中的环磷酸腺苷水平并抑制蛋白质磷酸化。

Antithrombotic nipecotamide increases cyclic AMP levels and inhibits protein phosphorylation in human platelets.

作者信息

Handa R K, Dillingham E O, Gollamudi R

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.

出版信息

Life Sci. 1995;57(10):983-8. doi: 10.1016/0024-3205(95)02033-f.

DOI:10.1016/0024-3205(95)02033-f

PMID:7643723

Abstract

alpha,alpha'-bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene dihydrobromide (A-1), a typical antithrombotic nipecotamide, elevated the levels of cyclic adenosine monophosphate (cAMP) in human platelets in vitro, without inhibiting cAMP-phosphodiesterase (PDE). The compound elevated the basal cAMP levels, enhanced the prostaglandin (PG)E1-stimulated platelet adenylyl cyclase (AC) activity, and prevented the ADP-induced decline of the latter. Collagen-induced phosphorylation of 20 and 47 kDa proteins was inhibited by IC50 and 0.5 x IC50 concentrations. In light of the known actions of A-1, it is suggested that stimulation of AC and inhibition of agonist-induced rise in cytosolic ionized calcium ([Ca2+]i) may constitute an aspect of its mechanism of action.

摘要

α,α'-双[3-(N,N-二乙基氨基甲酰基)哌啶基]-对二甲苯二氢溴化物(A-1)，一种典型的抗血栓形成的烟酰胺，在体外可提高人血小板中环磷酸腺苷(cAMP)的水平，而不抑制cAMP磷酸二酯酶(PDE)。该化合物提高了基础cAMP水平，增强了前列腺素(PG)E1刺激的血小板腺苷酸环化酶(AC)活性，并阻止了ADP诱导的后者活性下降。胶原蛋白诱导的20 kDa和47 kDa蛋白的磷酸化被IC50和0.5×IC50浓度所抑制。鉴于A-1的已知作用，提示刺激AC和抑制激动剂诱导的胞质游离钙离子([Ca2+]i)升高可能构成其作用机制的一个方面。