血管活性肠肽可提高血小板环磷酸腺苷（cAMP）水平，并抑制体外由血小板活化因子（PAF）诱导的血小板活化。

VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF).

作者信息

Cox C P, Linden J, Said S I

出版信息

Peptides. 1984 Mar-Apr;5(2):325-8. doi: 10.1016/0196-9781(84)90228-6.

PMID:6206481

Abstract

Platelet-activating factor (PAF), a potent endogenous phospholipid released by a variety of mammalian cells, induces platelet activation in vivo and in vitro. Little is known, however, about the physiological modulation of its actions. We have examined the ability of two naturally occurring compounds which stimulate cAMP production, vasoactive intestinal peptide (VIP) and prostacyclin (PGI2), to inhibit PAF-induced platelet aggregation and secretion in vitro. Washed, [3H]serotonin-labeled, rabbit platelets were incubated 60 sec in the presence of VIP, PGI2 or 3-isobutyl-1-methylxanthine (IBMX) and subsequently stimulated with PAF. In separate studies, cAMP levels were determined in similar aliquots of platelets incubated for 30 sec with VIP, PGI2 or IBMX. VIP, PGI2 and IBMX inhibited platelet aggregation and secretion in a dose-dependent manner. Fifty percent inhibition was achieved at final concentrations of 1.7 X 10(6) M VIP, 3.6 X 10(6) M PGI2 and 6.5 X 10(5) M IBMX. IBMX potentiated the inhibitory effects of VIP and PGI2 on PAF-induced platelet activation. VIP and PGI2 elevated platelet cAMP levels four-fold and 50-fold, respectively, in the presence of 10(3) M IBMX. These findings demonstrate that VIP inhibits PAF-induced platelet activation, with a potency comparable to that of PGI2.

摘要

血小板活化因子（PAF）是一种由多种哺乳动物细胞释放的强效内源性磷脂，可在体内和体外诱导血小板活化。然而，关于其作用的生理调节知之甚少。我们研究了两种能刺激环磷酸腺苷（cAMP）生成的天然化合物，即血管活性肠肽（VIP）和前列环素（PGI2），在体外抑制PAF诱导的血小板聚集和分泌的能力。将洗涤过的、用[3H]血清素标记的兔血小板在VIP、PGI2或3-异丁基-1-甲基黄嘌呤（IBMX）存在的情况下孵育60秒，随后用PAF刺激。在单独的研究中，测定了与VIP、PGI2或IBMX孵育30秒的类似血小板等分试样中的cAMP水平。VIP、PGI2和IBMX以剂量依赖的方式抑制血小板聚集和分泌。在最终浓度为1.7×10⁻⁶ M VIP、3.6×10⁻⁶ M PGI2和6.5×10⁻⁵ M IBMX时可实现50%的抑制。IBMX增强了VIP和PGI2对PAF诱导的血小板活化的抑制作用。在10⁻³ M IBMX存在的情况下，VIP和PGI2分别使血小板cAMP水平提高了四倍和五十倍。这些发现表明，VIP抑制PAF诱导的血小板活化，其效力与PGI2相当。