硫化氢调节大鼠空肠的收缩功能。
Hydrogen sulfide modulates contractile function in rat jejunum.
机构信息
Department of Surgery and Gastroenterology Research Unit, Mayo Clinic, Rochester, Minnesota 55902, USA.
出版信息
J Surg Res. 2012 Jun 15;175(2):234-42. doi: 10.1016/j.jss.2011.03.069. Epub 2011 Apr 22.
BACKGROUND
Effects of hydrogen sulfide (H(2)S), a third gasotransmitter of the gut, are not well understood. The aim of this study was to determine effects/mechanisms of H(2)S action on contractile function in rat jejunal muscle.
METHODS
Transmural strips of longitudinal muscle were evaluated. Response to sodium hydrosulfide (NaHS, H(2)S donor; 10(-5)-10(-3)M) was studied on spontaneous contractile activity and after precontraction (bethanechol, 3 × 10(-6)M). Atropine, propranolol, phentolamine, tetrodotoxin, capsaicin, L-N(G)-nitro arginine (L-NNA), and glibenclamide were used to determine mechanisms. L-cysteine (10(-4)-10(-2)M; substrate for H(2)S production) and aminooxyacetic acid and DL-propargylglycine (inhibitors of enzymes generating H(2)S endogenously) were used to study endogenous production. Aminooxyacetic acid, DL-propargylglycine, L-NNA, and vasoactive intestinal polypeptide (VIP) antagonist [D-p-Cl-Phe(6),Leu(17)]-VIP were used to study H(2)S release during electrical field stimulation (EFS) and interaction with VIP and nitric oxide. Immunohistofluorescence of jejunal whole mounts was performed for endogenous H(2)S-producing enzymes.
RESULTS
Cystathionine-β-synthase and cystathionine-γ-lyase were expressed only in myenteric plexus. NaHS suppressed spontaneous and stimulated contractile activity (P < 0.01). Glibenclamide prevented some suppression by NaHS (P = 0.01) of stimulated contractile activity but did not prevent suppression of spontaneous contractile activity. Other drugs had no effect on spontaneous contractile activity but increased inhibitory effects of NaHS on spontaneous and stimulated contractile activity (P < 0.05). L-cysteine had no effects on contractile activity. Inhibitors altered basal and stimulated activity suggesting endogenous release of H(2)S.
CONCLUSIONS
H(2)S presumably suppresses contractile activity in jejunum by direct effects on smooth muscle. Mechanism(s) of inhibition remains unclear, because blocking known neurotransmitters enhanced H(2)S-induced suppression, while blocking adenosine triphosphate (ATP)-sensitive K(+)-channels did not block H(2)S-induced inhibition.
背景
肠道的第三种气体递质硫化氢（H₂S）的作用尚不清楚。本研究旨在确定 H₂S 对大鼠空肠平滑肌收缩功能的作用及其机制。
方法
采用纵行肌跨壁肌条评价。研究了 NaHS（H₂S 供体；10⁻⁵-10⁻³M）对自发性收缩活动和预收缩（丁酰胆碱，3×10⁻⁶M）的影响。用阿托品、普萘洛尔、酚妥拉明、河豚毒素、辣椒素、L-N（G）-硝基精氨酸（L-NNA）和格列本脲来确定机制。用 L-半胱氨酸（10⁻⁴-10⁻²M；H₂S 产生的底物）和氨基氧乙酸和 DL-丙炔甘氨酸（内源性产生 H₂S 的酶抑制剂）来研究内源性产生。用氨基氧乙酸、DL-丙炔甘氨酸、L-NNA 和血管活性肠肽（VIP）拮抗剂 [D-p-Cl-Phe（6），Leu（17）]-VIP 研究电刺激（EFS）时 H₂S 的释放及其与 VIP 和一氧化氮的相互作用。进行空肠全层免疫荧光以检测内源性产生 H₂S 的酶。
结果
胱硫醚-β-合酶和胱硫醚-γ-裂合酶仅在肌间神经丛中表达。NaHS 抑制自发性和刺激收缩活动（P<0.01）。格列本脲可预防 NaHS 对刺激收缩活动的部分抑制（P=0.01），但不能预防自发性收缩活动的抑制。其他药物对自发性收缩活动没有影响，但增加了 NaHS 对自发性和刺激收缩活动的抑制作用（P<0.05）。L-半胱氨酸对收缩活动没有影响。抑制剂改变了基础和刺激活性，提示内源性释放 H₂S。
结论
H₂S 可能通过直接作用于平滑肌来抑制空肠的收缩活动。抑制的机制尚不清楚，因为阻断已知的神经递质增强了 H₂S 诱导的抑制作用，而阻断三磷酸腺苷（ATP）敏感性钾（K+）通道并不阻断 H₂S 诱导的抑制作用。
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