Olgart C, Hallén K, Wiklund N P, Iversen H H, Gustafsson L E
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Acta Physiol Scand. 1998 Jan;162(1):89-95. doi: 10.1046/j.1365-201X.1998.0274f.x.
The role of soluble guanylyl cyclase in nitrergic inhibitory neuroeffector transmission was investigated in the longitudinal muscle from guinea-pig colon, by using an inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). In preparations precontracted with histamine, electrical field stimulation (EFS) or exogenous nitric oxide (NO) induced relaxations. The relaxation induced by NO-application was abolished by ODQ. Both ODQ and the NO-synthase inhibitor N omega-nitro-L-arginine (L-NOARG) partially inhibited the EFS-evoked relaxation to a similar extent. These effects were dose-dependent. The inhibition was more pronounced in the late phase of the EFS-induced relaxation. The inhibitory effect of ODQ on EFS-induced relaxation was not affected by additional application of L-NOARG. When NO-formation was blocked by L-NOARG, a subsequent addition of ODQ gave no further inhibition of the relaxation. These findings suggest that inhibitory non-adrenergic, non-cholinergic neurotransmission in guinea-pig colon is dependent on endogenous formation of NO, and that the NO-effect is exclusively mediated via the soluble guanylyl cyclase pathway. The existence of an NO-independent inhibitory transmission, which is not mediated through the cyclic GMP pathway, is also indicated. Furthermore, it is demonstrated that the NO/soluble guanylyl cyclase-independent transmission has an earlier onset as compared with the NO/soluble guanylyl cyclase-dependent pathway.
通过使用可溶性鸟苷酸环化酶抑制剂1H-[1,2,4]恶二唑并[4,3,-a]喹喔啉-1-酮（ODQ），研究了可溶性鸟苷酸环化酶在豚鼠结肠纵行肌中氮能抑制性神经效应传递中的作用。在预先用组胺预收缩的制剂中，电场刺激（EFS）或外源性一氧化氮（NO）可引起舒张。ODQ可消除NO应用所诱导的舒张。ODQ和NO合酶抑制剂Nω-硝基-L-精氨酸（L-NOARG）均部分抑制EFS诱发的舒张，且程度相似。这些效应呈剂量依赖性。在EFS诱导舒张的后期，抑制作用更为明显。ODQ对EFS诱导舒张的抑制作用不受额外应用L-NOARG的影响。当L-NOARG阻断NO形成后，随后添加ODQ不再进一步抑制舒张。这些发现表明，豚鼠结肠中的抑制性非肾上腺素能、非胆碱能神经传递依赖于内源性NO的形成，且NO的作用完全通过可溶性鸟苷酸环化酶途径介导。还表明存在一种不依赖NO的抑制性传递，其不通过环鸟苷酸途径介导。此外，已证明与依赖NO/可溶性鸟苷酸环化酶的途径相比，不依赖NO/可溶性鸟苷酸环化酶的传递起效更早。
