Maule A G, Geary T G, Bowman J W, Marks N J, Blair K L, Halton D W, Shaw C, Thompson D P
Upjohn Company, Kalamazoo, MI 49001, USA.
Invert Neurosci. 1995 Dec;1(3):255-65. doi: 10.1007/BF02211027.
A large number of FMRFamide-related peptides (FaRPs) are found in nematodes, and some of these are known to influence tension and contractility of neuromuscular strips isolated from Ascaris suum body wall. Relaxation of these strips has been noted with five nematode FaRPs. The inhibitory actions of SDPNFLRFamide (PF1) and SADPNFLRFamide (PF2) appear to be mediated by nitric oxide, as previously demonstrated with inhibitors of nitric oxide synthase (NOS). This present study showed that the effects of PF1 were also depended on external Ca++ and were reduced by the Ca(++)-channel blocker verapamil, observations consistent with the finding that nematode NOS is Ca(++)-dependent. KSAYMRFamide (PF3), KNIRFamide (PF4) and KNAFIRFamide (an alanine substituted analog of KNEFIRFamide, AF1, termed A3AF1) also relaxed A. suum muscle strips, but these responses were not affected by NOS inhibitors. PF3 inhibited the activity of strips prepared from the dorsal side of the worm, but contracted ventral strips. Both effects were dependent on the presence of ventral/dorsal nerve cords (unlike PF1/PF2) and were attenuated in medium which contained high K+ or low Ca++. PF4-induced muscle relaxation and hyperpolarization were independent of nerve cords, but were reversed in Cl-free medium, unlike PF1 or PF3. The PF4 effect physiologically desensitized muscle strips to subsequent treatment with PF4 and/or GABA. However, PF4 and GABA were not synergistic in this preparation. The effects of GABA, but not PF4, were reduced in muscle strips treated with the GABA antagonist, NCS 281-93. Following PF4 (or GABA) relaxation, subsequent treatment with higher doses of PF4 caused muscle strip contraction. A3AF1 was found to relax muscle strips and hyperpolarize muscle cells independently of the ventral and dorsal nerve cords, K+, Ca++, and Cl-, and mimicked the inhibitory phase associated with the exposure of these strips to AF1. On the basis of anatomical and ionic dependence, these data have delineated at least four distinct inhibitory activities attributable to nematode FaRPs. Clearly, a remarkably complex set of inhibitory mechanisms operate in the nematode neuromuscular system.
在 nematodes 中发现了大量与 FMRFamide 相关的肽（FaRPs），其中一些已知会影响从猪蛔虫体壁分离出的神经肌肉条带的张力和收缩性。已注意到五种线虫 FaRPs 可使这些条带松弛。如先前用一氧化氮合酶（NOS）抑制剂所证明的，SDPNFLRFamide（PF1）和 SADPNFLRFamide（PF2）的抑制作用似乎由一氧化氮介导。本研究表明，PF1 的作用也依赖于细胞外 Ca++，并且会被 Ca(++)通道阻滞剂维拉帕米减弱，这些观察结果与线虫 NOS 是 Ca(++)依赖性的这一发现一致。KSAYMRFamide（PF3）、KNIRFamide（PF4）和 KNAFIRFamide（KNEFIRFamide 的丙氨酸取代类似物，AF1，称为 A3AF1）也可使猪蛔虫肌肉条带松弛，但这些反应不受 NOS 抑制剂影响。PF3 抑制从蠕虫背侧制备的条带的活性，但使腹侧条带收缩。两种作用均依赖于腹侧/背侧神经索的存在（与 PF1/PF2 不同），并且在含有高 K+或低 Ca++的培养基中减弱。PF4 诱导的肌肉松弛和超极化与神经索无关，但与 PF1 或 PF3 不同，在无 Cl-的培养基中会逆转。PF4 的作用在生理上使肌肉条带对随后用 PF4 和/或 GABA 的处理产生脱敏。然而，在该制剂中 PF4 和 GABA 没有协同作用。在用 GABA 拮抗剂 NCS 281 - 93 处理的肌肉条带中，GABA 的作用减弱，但 PF4 的作用未减弱。在 PF4（或 GABA）使肌肉条带松弛后，随后用更高剂量的 PF4 处理会导致肌肉条带收缩。发现 A3AF1 可使肌肉条带松弛并使肌肉细胞超极化，且与腹侧和背侧神经索、K+、Ca++和 Cl-无关，并模拟了这些条带暴露于 AF1 时相关的抑制阶段。基于解剖学和离子依赖性，这些数据至少描绘了线虫 FaRPs 可导致的四种不同的抑制活性。显然，线虫神经肌肉系统中存在一组非常复杂的抑制机制。
