Rakestraw P C, Snyder J R, Woliner M J, Sanders K M, Shuttleworth C W
Department of Surgical and Radiological Sciences, University of California, Davis 95616, USA.
Am J Vet Res. 1996 Aug;57(8):1206-13.
To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle.
Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists L-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde fixed tissue.
Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contratile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 microM) and apamin (0.3 microM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 microM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 +/- 6.3% reduction at approximately 0.3 microM, n = 16). Antagonism of NO synthesis did not alter the response to VIP.
NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle.
These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO.
评估一氧化氮（NO）、血管活性肠肽（VIP）以及一种通过蜂毒明肽敏感机制起作用的递质在介导马空肠环行肌抑制性传递中的作用，并确定肌间神经丛和环行肌中产生VIP和NO的神经纤维的分布。
将环行肌条悬挂于含有氧合改良克雷布斯溶液的组织浴中，并连接到等长力换能器上。测试对电场刺激（EFS）、河豚毒素、NO拮抗剂L-N-硝基精氨酸甲酯（L-NAME）和N-硝基-L-精氨酸、蜂毒明肽、VIP、纯NO以及NO供体硝普钠的反应。对多聚甲醛固定的组织进行VIP样免疫染色和NADPH黄递酶组织化学染色。
肌间神经元和环行肌中的神经纤维亚群对NADPH黄递酶和VIP样染色呈阳性。EFS引起收缩活动的频率依赖性抑制。河豚毒素可阻止EFS诱导的收缩抑制。在大多数测试频率下，L-NAME（200微摩尔）和蜂毒明肽（0.3微摩尔）显著（P<0.01）降低EFS刺激的收缩活动抑制。L-NAME和蜂毒明肽的作用是相加的。在它们共同存在时，EFS诱导兴奋而非抑制（5赫兹时增加196.7%，n=28，P<0.01）。硝普钠模拟了EFS对收缩活动的抑制。纯NO（3-6微摩尔）消除了收缩活动。VIP诱导了收缩活动的剂量依赖性抑制（约0.3微摩尔时降低89.1±6.3%，n=16）。NO合成的拮抗作用未改变对VIP的反应。
NO、VIP以及一种通过蜂毒明肽敏感机制起作用的物质似乎共同介导马空肠环行肌的抑制性传递。
这些发现可能为运动障碍提示新的治疗靶点，例如抑制NO合成或作用的药物。
