Rattan S, Chakder S
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Am J Physiol. 1993 Oct;265(4 Pt 1):G799-804. doi: 10.1152/ajpgi.1993.265.4.G799.
We examined the effect and role of CO in opossum internal anal sphincter (IAS) relaxation in response to nonadrenergic noncholinergic (NANC) nerve stimulation. Effects of NANC nerve stimulation on the IAS tension and second messengers (cAMP and cGMP) were examined before and after the selective heme oxygenase (HO) inhibitor zinc protoporphyrin IX (Zn PP-IX). The HO activity of the IAS smooth muscle was determined before and after NANC nerve stimulation. CO caused a concentration-dependent and tetrodotoxin-resistant fall in the resting tension of the IAS. The direct action of CO was confirmed by its relaxant action on the isolated smooth muscle cells. Furthermore, CO caused an increase in the tissue cGMP levels comparable to that observed with nerve stimulation. Zn PP-IX caused suppression of IAS relaxation caused by NANC nerve stimulation and vasoactive intestinal polypeptide (VIP) but not by peptide histidine-isoleucine and suppression of the increase in cGMP in response to NANC nerve stimulation. Zn PP-IX had no significant effect on the IAS responses to CO, nitric oxide (NO), and the beta-adrenoceptor agonist isoproterenol. The IAS responses to CO were not modified by the NO synthase inhibitor NG-nitro-L-arginine. Significant HO activity was detected in the IAS, which increased further in response to NANC nerve stimulation and VIP. The direct relaxant actions of CO and the suppression of NANC-mediated relaxation of the IAS by the HO inhibitor suggest the involvement of CO in the neurally mediated IAS relaxation.
我们研究了一氧化碳（CO）在负鼠肛门内括约肌（IAS）对非肾上腺素能非胆碱能（NANC）神经刺激产生松弛反应中的作用及影响。在使用选择性血红素加氧酶（HO）抑制剂原卟啉锌IX（Zn PP-IX）前后，检测了NANC神经刺激对IAS张力和第二信使（cAMP和cGMP）的影响。测定了NANC神经刺激前后IAS平滑肌的HO活性。CO可使IAS的静息张力呈浓度依赖性且对河豚毒素不敏感地下降。CO对分离的平滑肌细胞的舒张作用证实了其直接作用。此外，CO可使组织cGMP水平升高，与神经刺激时观察到的情况相当。Zn PP-IX可抑制NANC神经刺激和血管活性肠肽（VIP）引起的IAS松弛，但对肽组氨酸异亮氨酸引起的松弛无抑制作用，且可抑制NANC神经刺激引起的cGMP升高。Zn PP-IX对IAS对CO、一氧化氮（NO）和β-肾上腺素能受体激动剂异丙肾上腺素的反应无显著影响。NO合酶抑制剂NG-硝基-L-精氨酸未改变IAS对CO的反应。在IAS中检测到显著的HO活性，其在NANC神经刺激和VIP作用下进一步升高。CO的直接舒张作用以及HO抑制剂对NANC介导的IAS松弛的抑制作用表明CO参与了神经介导的IAS松弛。
