Calderaro V, Parrillo C, Giovane A, Greco R, Matera M G, Berrino L, Rossi F
Institute of Pharmacology and Toxicology, First Faculty of Medicine, University of Naples, Federico II, Italy.
J Pharmacol Exp Ther. 1992 Nov;263(2):579-87.
Antiflammins are synthetic peptides with sequence homology to proteins inhibitory for phospholipase A2. The effects of antiflammins on chloride secretion induced by the calcium ionophore A23187, arachidonic acid (AA) and prostaglandin E2 (PGE2) were investigated in distal rabbit colonic mucosa mounted in Ussing-type chambers. 100 nM AF-2 (antiflammin 2, peptide HDMNKVLDL) fully prevented the increase in Isc, net chloride secretion, tissue PGE2 and second messenger cAMP induced by 5 microM A23187. AF-1 (antiflammin 1, peptide MQMKKVLDS) also inhibited, although to a lesser extent, the A23187-mediated increase in Isc. AF-2 inhibition began at doses of 100 nM (delta Isc -0.20 +/- 0.08, microEq h-1 cm-2, mean +/- S.E.M., N = 3) and was maximal at doses comprised between 200 and 250 nM (delta Isc -0.51 +/- 0.12, microEq h-1 cm-2, mean +/- S.E.M., N = 3). AF-2 also inhibited the increase in Isc and chloride secretion induced by the incubation with 10 microM AA and bradykinin but it was ineffective when tissues were stimulated with 10 microM PGE2. 100 nM AF-2 brought about an inhibition of the increase in AA-mediated increases in PGs and cAMP comparable to that of 10 microM of the cyclooxygenase inhibitor indomethacin. In vitro assay of colonic cyclooxygenase activity showed that 100 nM AF-2 and AF-1 inhibited cyclooxygenase activity (73 and approximately 30%, respectively), but they did not modify the in vitro activity of porcine phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)
抗炎症肽是与抑制磷脂酶A2的蛋白质具有序列同源性的合成肽。在置于尤斯灌流小室的兔远端结肠黏膜中，研究了抗炎症肽对钙离子载体A23187、花生四烯酸（AA）和前列腺素E2（PGE2）诱导的氯离子分泌的影响。100 nM的AF - 2（抗炎症肽2，肽HDMNKVLDL）完全阻止了5 microM A23187诱导的短路电流（Isc）增加、净氯离子分泌、组织PGE2和第二信使环磷酸腺苷（cAMP）的增加。AF - 1（抗炎症肽1，肽MQMKKVLDS）也有抑制作用，尽管程度较小，可抑制A23187介导的Isc增加。AF - 2在100 nM剂量时开始产生抑制作用（Isc变化量为 - 0.20±0.08，微当量·小时-1·厘米-2，平均值±标准误，N = 3），在200至250 nM剂量时达到最大抑制效果（Isc变化量为 - 0.51±0.12，微当量·小时-1·厘米-2，平均值±标准误，N = 3）。AF - 2还抑制了与10 microM AA和缓激肽孵育诱导的Isc和氯离子分泌增加，但在用10 microM PGE2刺激组织时无效。100 nM AF - 2对AA介导的前列腺素和cAMP增加的抑制作用与10 microM环氧化酶抑制剂吲哚美辛相当。结肠环氧化酶活性的体外测定表明，100 nM AF - 2和AF - 1抑制环氧化酶活性（分别为73%和约30%），但它们不改变猪磷脂酶A2的体外活性。（摘要截短于250字）
