El Sayah Mariem, Calixto João B
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, Florianópolis, SC 88015-420, Brazil.
Peptides. 2003 Jul;24(7):1045-51. doi: 10.1016/s0196-9781(03)00182-7.
We have reported previously that bradykinin (BK) induces potent and reproducible concentration-dependent contractions of the pig iris sphincter (PIS) muscle in vitro through the activation of BK B(2) receptors. Here we attempted to investigate additional mechanisms by which BK induces contraction of the PIS in vitro. BK-mediated contraction of the PIS relied largely on the external Ca2+ influx by a mechanism sensitive to the L-, N- and P-type of Ca2+ channel selective blockers. Likewise, BK-induced contraction of the PIS was greatly inhibited by the CGRP-(8-37), NK(2) or NK(3) receptor antagonists (SR 48968, SR 142801), and to a lesser extent by the NK(1) antagonist (FK 888). Capsaicin desensitization of PIS or capsazepine pre-incubation also significantly reduced BK-mediated contraction in the PIS. Furthermore, KT 5720 or GF 109203X (the protein kinase A and C inhibitors, respectively) also significantly inhibited BK-mediated contraction. Taken together, these results indicate that BK-mediated contraction of the PIS seems to be mediated primarily by the release of CGRP and tachykinins from sensory nerve fibers, and relies largely on extracellular Ca2+ influx via activation of L-, N- and P-type of Ca2+ channels. Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms.
我们之前曾报道，缓激肽（BK）在体外通过激活BK B(2)受体，可诱导猪虹膜括约肌（PIS）肌肉产生强效且可重复的浓度依赖性收缩。在此，我们试图研究BK在体外诱导PIS收缩的其他机制。BK介导的PIS收缩在很大程度上依赖于细胞外Ca2+内流，其机制对L型、N型和P型Ca2+通道选择性阻滞剂敏感。同样，CGRP-(8 - 37)、NK(2)或NK(3)受体拮抗剂（SR 48968、SR 142801）可显著抑制BK诱导的PIS收缩，而NK(1)拮抗剂（FK 888）的抑制作用较小。辣椒素使PIS脱敏或预先孵育辣椒平也可显著降低BK介导的PIS收缩。此外，KT 5720或GF 109203X（分别为蛋白激酶A和C抑制剂）也可显著抑制BK介导的收缩。综上所述，这些结果表明，BK介导的PIS收缩似乎主要由感觉神经纤维释放CGRP和速激肽介导，并且在很大程度上依赖于通过激活L型、N型和P型Ca2+通道的细胞外Ca2+内流。最后，这些反应是由蛋白激酶A和C依赖性机制的激活介导的。
