Handa R K, Dillingham E O, Gollamudi R
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis 38163, USA.
Life Sci. 1995;57(10):983-8. doi: 10.1016/0024-3205(95)02033-f.
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.
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。
