Torphy T J, Fine C F, Burman M, Barnette M S, Ormsbee H S
Am J Physiol. 1986 Dec;251(6 Pt 1):G786-93. doi: 10.1152/ajpgi.1986.251.6.G786.
Experiments were conducted to determine whether relaxation of the opossum isolated lower esophageal sphincter (LES), induced by electrical field stimulation (EFS) or various pharmacological agents, is associated with changes in cyclic nucleotide content. EFS relaxed the LES in a frequency-dependent manner with 0.7 Hz producing half-maximal relaxation. Control tissues and tissues stimulated at various frequencies were clamp-frozen and assayed for cyclic nucleotide content. EFS had no effect on adenosine 3',5'-cyclic monophosphate (cAMP) content but increased guanosine 3',5'-cyclic monophosphate (cGMP) content in a frequency-dependent manner. Tetrodotoxin eliminated both the relaxation and cGMP accumulation in response to EFS. Vasoactive intestinal polypeptide (VIP) relaxed the LES with an EC50 of 0.1 microM. In contrast to the results with EFS, VIP enhanced cAMP content but had no effect on cGMP content. Relaxation of the LES produced by sodium nitroprusside or atriopeptin II was accompanied by an increase in cGMP accumulation, whereas isoproterenol- and dopamine-induced relaxation was accompanied by an increase in cAMP content. The data indicate that, depending on the stimulus, increases in either cAMP or cGMP content can accompany LES relaxation. These results are consistent with the proposed role of cyclic nucleotides as second messengers mediating LES relaxation.
进行实验以确定由电场刺激（EFS）或各种药物诱导的负鼠离体下食管括约肌（LES）松弛是否与环核苷酸含量的变化有关。EFS以频率依赖性方式松弛LES，0.7Hz产生最大松弛的一半。将对照组织和以不同频率刺激的组织夹冻并测定环核苷酸含量。EFS对腺苷3',5'-环磷酸（cAMP）含量没有影响，但以频率依赖性方式增加鸟苷3',5'-环磷酸（cGMP）含量。河豚毒素消除了对EFS的松弛和cGMP积累。血管活性肠肽（VIP）以0.1μM的EC50松弛LES。与EFS的结果相反，VIP增加cAMP含量但对cGMP含量没有影响。硝普钠或心房肽II诱导的LES松弛伴随着cGMP积累的增加，而异丙肾上腺素和多巴胺诱导的松弛伴随着cAMP含量的增加。数据表明，根据刺激的不同，cAMP或cGMP含量的增加可伴随LES松弛。这些结果与环核苷酸作为介导LES松弛的第二信使的提议作用一致。
