Osthaus L E, Galligan J J
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
J Pharmacol Exp Ther. 1992 Jan;260(1):140-5.
Enteric inhibitory nerves release nonadrenergic, noncholinergic (NANC) transmitters onto the muscle layers of guinea pig ileum. Nitric oxide (NO), released from endothelial cells, relaxes vascular smooth muscle and NO may also be a chemical messenger released from neurons. The present study investigated the possibility that NO is a NANC transmitter in guinea pig ileum longitudinal muscle myenteric plexus. Segments of longitudinal muscle myenteric plexus were maintained in scopolamine-containing (1 microM) Krebs' solution. Histamine (1 microM) was used to induce tone, and NANC relaxations were produced by trains of transmural electrical stimuli. NANC responses consisted of a fast relaxation (approximately 1 s duration) followed either by a slow relaxation or a slow contraction (approximately 4 s duration). The NO-synthase inhibitors, NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, inhibited peak (fast) neurogenic relaxations by a maximum of 62 +/- 6%, 91 +/- 3% and 50 +/- 3%, respectively. NO-synthase inhibitors either completely blocked the slow relaxation revealing a late contraction or increased the amplitude of late contractions. The actions of NG-monomethyl-L-arginine were partially reversed by L-arginine (1 mM) while the actions of NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine were not consistently reversed by L-arginine. L-Arginine itself did not alter neurogenic responses. NG-monomethyl-D-arginine (10-300 microM) did not affect NANC relaxations or contractions. Hemoglobin (10 microM) inhibited peak NANC relaxations by 45 +/- 4% and increased the amplitude of late contractions without affecting papaverine-induced relaxations. Sodium nitroprusside and 8-bromo-cyclic guanosine monophosphate mimicked NANC relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
肠抑制神经将非肾上腺素能、非胆碱能（NANC）递质释放到豚鼠回肠的肌层上。内皮细胞释放的一氧化氮（NO）可使血管平滑肌松弛，并且NO也可能是神经元释放的一种化学信使。本研究调查了NO是豚鼠回肠纵行肌肌间神经丛中NANC递质的可能性。纵行肌肌间神经丛节段置于含东莨菪碱（1微摩尔）的 Krebs 溶液中。组胺（1微摩尔）用于诱导张力，经壁电刺激串引发NANC舒张。NANC反应包括快速舒张（持续约1秒），随后是缓慢舒张或缓慢收缩（持续约4秒）。NO合酶抑制剂NG-单甲基-L-精氨酸、NG-硝基-L-精氨酸和NG-硝基-L-精氨酸甲酯分别最大程度地抑制峰值（快速）神经源性舒张62±6%、91±3%和50±3%。NO合酶抑制剂要么完全阻断缓慢舒张而显示出后期收缩，要么增加后期收缩的幅度。L-精氨酸（1毫摩尔）可部分逆转NG-单甲基-L-精氨酸的作用，而L-精氨酸不能始终如一地逆转NG-硝基-L-精氨酸甲酯和NG-硝基-L-精氨酸的作用。L-精氨酸本身不改变神经源性反应。NG-单甲基-D-精氨酸（10 - 300微摩尔）不影响NANC舒张或收缩。血红蛋白（10微摩尔）抑制峰值NANC舒张45±4%，并增加后期收缩的幅度，而不影响罂粟碱诱导的舒张。硝普钠和8-溴环鸟苷单磷酸模拟NANC舒张。（摘要截短于250字）
