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Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles

机译：Ghrelin是虹膜括约肌和扩张肌的一种新型局部产生的松弛肽

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摘要

Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1-5 human ghrelin (frGhr, 10(-9)-6 x 10(-5)M) and 1-5 human des-octanoyl-ghrelin (d-frGhr; 10(-9)-6 x 10(-5)M) were tested on iris rabbit sphincter (n=11 frGhr; n=7 d-frGhr), dilator (n=6 frGhr; n=6 d-frGhr) and rat sphincter (n=6 frGhr; n=8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10(-5)M; n=7); ii) indomethacin (10(-5)M; n=7); iii) DLys(3)GHRP6 (10(-4)M; n=6); and iv) apamin+carybdotoxin (10(-6)M; n=6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys(3)GHRP6 (10(-4)M; n=7). Finally, ghrelin mRNA production was assessed by "in situ" hybridization in Wistar rat eyes (n=8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 x 10(-5)M, 1.5-3 min after its addition, decreasing tension by 34.1+/-12.1%, 25.8+/-4.8% and 52.1+/-10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys(3)GHRP6 (118.1+/-21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin+carybdotoxin (36.4+/-14.4%) or L-NA (52.4+/-11.4%). Relaxing effects of d-frGhr in rabbit (43.3+/-5.2%) and rat (77.1+/-15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K(Ca) channels.
机译：Ghrelin是一种最近描述的酰化肽，可作为体糖代谢物，并已描述对平滑肌，骨骼肌和心肌的作用。我们检查了ghrelin的产生及其对虹膜肌肉松弛的影响。 1-5人生长素释放肽（frGhr，10（-9）-6 x 10（-5）M）和1-5人去辛酰基-生长素释放肽（d-frGhr; 10（-9）-6 x 10的收缩作用（-5）M）在虹膜兔括约肌（n = 11 frGhr; n = 7 d-frGhr），扩张器（n = 6 frGhr; n = 6 d-frGhr）和大鼠括约肌（n = 6 frGhr; n = 8 d-frGhr）预收缩的肌肉。在以下情况下也测试了frGhr对兔子括约肌的作用：i）L-NA（10（-5）M; n = 7）; ii）消炎痛（10（-5）M; n = 7）; iii）DLys（3）GHRP6（10（-4）M; n = 6）; iv）apamin + carybdotoxin（10（-6）M; n = 6）。此外，在兔扩张器上，在DLys（3）GHRP6（10（-4）M; n = 7）存在下测试了frGhr的作用。最后，通过“原位”杂交在Wistar大鼠眼中评估生长素释放肽mRNA的产生（n ＝ 8）。在所有肌肉中，frGhr促进了浓度依赖性的放松，在添加后的1.5-3分钟内最大浓度为6 x 10（-5）M，使张力降低了34.1 +/- 12.1％，25.8 +/- 4.8％和52.1+在兔括约肌，扩张器和大鼠括约肌中分别为/-10.3%。在兔括约肌中，frGhr的松弛作用为：（i）在DLys（3）GHRP6（118.1 +/- 21.1％）的存在下增强； （ii）被消炎痛钝化； （iii）不会被阿帕明+核毒素（36.4 +/- 14.4％）或L-NA（52.4 +/- 11.4％）所改变。 d-frGhr在兔（43.3 +/- 5.2％）和大鼠（77.1 +/- 15.3％）的括约肌中的放松作用与frGhr相似。在兔扩张肌中，d-frGhr并未显着改变活动张力，而GHSR-1a阻滞使frGhr的松弛作用减弱。在虹膜后上皮中鉴定出Ghrelin mRNA。总之，ghrelin是虹膜扩张器和括约肌的一种新型，局部产生的松弛剂，这种作用在前者中由GHSR-1a介导，而在后者中则不是。此外，在括约肌中它似乎是由前列腺素介导的，而不是由NO或K（Ca）通道介导的。

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