前列腺素对牛和猫虹膜括约肌平滑肌中丝裂原活化蛋白激酶磷酸化、肌球蛋白轻链磷酸化及收缩作用的种属差异。

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

作者信息

Kaddour-Djebbar I, Ansari H R, Akhtar R A, Abdel-Latif A A

机构信息

Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2100, USA.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2005 Jan;72(1):49-57. doi: 10.1016/j.plefa.2004.10.001.

DOI:10.1016/j.plefa.2004.10.001

PMID:15589399

Abstract

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

摘要

我们自己实验室以及其他实验室的证据表明，EP受体配体是牛虹膜括约肌中的强效收缩激动剂，而FP受体激动剂是猫虹膜括约肌中的强效收缩激动剂。在此，我们研究了FP、EP、TP和DP类前列腺素（PG）受体激动剂对牛和猫虹膜括约肌中肌球蛋白轻链（MLC）磷酸化、p42/p44丝裂原活化蛋白激酶（MAP激酶）磷酸化及收缩的影响。通过三种信号转导机制检测，即MLC磷酸化、MAP激酶磷酸化和收缩检测，我们证明在牛虹膜括约肌中，PG激动剂在收缩和MLC磷酸化检测中的效力排序如下：E2>U46619>F2α>D2，而在猫中为F2α>D2>E2>U46619。在MAP激酶检测中，在牛虹膜括约肌中效力排序为E2>F2α，在猫中为F2α>E2。这些结论得到以下发现的支持：（1）在收缩检测中，在牛括约肌中，PGF2α、PGE2、U46619和PGD2的半数有效浓度（EC50）分别为1.4×10−7、5.0×10−9、9.0×10−9和1.3×10−6M，在猫中的相应值分别为1.9×10−8、2.3×10−7、1.5×10−6和6.9×10−8M。（2）在MLC磷酸化检测中，在牛括约肌中，PGF2α、PGE2、U46619和PGD2使MLC磷酸化分别增加118%、165%、153%和72%，在猫中的相应值分别为175%、99%、90%和95%。（3）在MAP激酶检测中，在牛虹膜括约肌中，PGF2α和PGE2使MAP激酶磷酸化分别增加276%和328%，在猫中的相应值分别为308%和245%。所呈现的数据表明，前列腺素对牛和猫虹膜中MLC激酶信号通路的影响存在明显的物种差异，并且进一步证实了牛虹膜中存在FP受体。