Moummi C, Rattan S
Harvard Thorndike Laboratory, Charles A. Dana Research Institute, Division of Gastroenterology, Beth Israel Hospital, Boston, Massachusetts.
Am J Physiol. 1988 Nov;255(5 Pt 1):G571-8. doi: 10.1152/ajpgi.1988.255.5.G571.
The present studies were performed in vitro to define the participation of regulatory cyclic nucleotides in the relaxation of internal anal sphincter (IAS) smooth muscle in response to neural stimulation by electrical field stimulation (EFS) vs. exogenous vasoactive intestinal peptide (VIP). EFS and VIP both caused relaxation of the resting tone in the opossum-isolated IAS smooth muscle strips. The addition of permeant cyclic nucleotide derivatives, the guanylate cyclase stimulant sodium nitroprusside (SNP), and the adenylate cyclase stimulant forskolin caused a dose-dependent fall in the resting tension of IAS smooth muscle. The inhibitory effect of the agonists on the IAS smooth muscle was not modified by tetrodotoxin (TTX), a neurotoxin. TTX almost abolished the IAS responses to EFS. The effects of SNP and forskolin were selectively blocked by the putative inhibitors of corresponding enzyme systems, i.e., methylene blue (MB) (3 X 10(-5) M) for guanylate cyclase and N-ethylmaleimide (NEM) (10(-4) M) in the case of adenylate cyclase. NEM and not MB caused significant antagonism of the fall in IAS tension in response to both EFS and VIP during the control experiments. Such data suggest a common biochemical link (adenosine 3',5'-cyclic monophosphate as second messenger system) between the IAS smooth muscle relaxations with neural stimulation and VIP. In addition, a part of the IAS smooth muscle relaxation in response to EFS also involves the mediation of guanosine 5'-cyclic monophosphate.
本研究在体外进行，以确定调节性环核苷酸在电场刺激（EFS）与外源性血管活性肠肽（VIP）引起的神经刺激下，内括约肌（IAS）平滑肌舒张中的作用。EFS和VIP均可使负鼠离体IAS平滑肌条的静息张力降低。添加渗透性环核苷酸衍生物、鸟苷酸环化酶刺激剂硝普钠（SNP）和腺苷酸环化酶刺激剂福斯高林，可使IAS平滑肌的静息张力呈剂量依赖性下降。激动剂对IAS平滑肌的抑制作用不受神经毒素河豚毒素（TTX）的影响。TTX几乎完全消除了IAS对EFS的反应。SNP和福斯高林的作用分别被相应酶系统的假定抑制剂选择性阻断，即鸟苷酸环化酶的亚甲蓝（MB）（3×10⁻⁵M）和腺苷酸环化酶的N-乙基马来酰亚胺（NEM）（10⁻⁴M）。在对照实验中，NEM而非MB对EFS和VIP引起的IAS张力下降有显著拮抗作用。这些数据表明，神经刺激和VIP引起的IAS平滑肌舒张之间存在共同的生化联系（腺苷3',5'-环一磷酸作为第二信使系统）。此外，EFS引起的IAS平滑肌舒张部分还涉及鸟苷5'-环一磷酸的介导。
