Terauchi Akiko, Kobayashi Daisuke, Mashimo Hiroshi
Center of Swallowing and Motility Disorders, Department of Veterans Affairs Medical Center, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G291-9. doi: 10.1152/ajpgi.00005.2005. Epub 2005 Apr 21.
Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS-/-), eNOS-deficient (eNOS-/-), and W/W(v) mice (lacking certain c-Kit-expressing ICC) with or without L-arginine or N(omega)-nitro-L-arginine methyl ester (L-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS-/- was higher and W/W(v) was lower than wild-type and nNOS-/- mice. L-arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS-/-, and W/W(v) mice. However, neither L-arginine nor L-NAME affected basal tone in eNOS-/- mice. In vitro, L-arginine decreased basal tone in wild-type and nNOS-/- IAS but not in eNOS-/- or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS-/-, and W/W(v) mice but absent in all nNOS-/- mice. EFS-induced IAS relaxation was also reduced in nNOS-/- IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.
一氧化氮（NO）可使肛门内括约肌（IAS）松弛，但其酶源尚不清楚；可能涉及神经元型（nNOS）和内皮型（eNOS）一氧化氮合酶（NOS）同工型。此外， Cajal间质细胞（ICC）可能参与IAS松弛。我们使用基因小鼠模型研究了nNOS、eNOS和表达c-Kit的ICC在IAS松弛中的相对作用。通过特制的固态测压探头在体内评估基础IAS张力和直肠肛门抑制反射（RAIR），并使用野生型、nNOS缺陷型（nNOS-/-）、eNOS缺陷型（eNOS-/-）和W/W(v)小鼠（缺乏某些表达c-Kit的ICC），对其进行或不进行L-精氨酸或N(ω)-硝基-L-精氨酸甲酯（L-NAME）处理。此外，在器官浴中使用野生型和突变型IAS研究基础张力和对电场刺激（EFS）的反应。在体内，eNOS-/-小鼠的基础张力高于野生型和nNOS-/-小鼠，而W/W(v)小鼠的基础张力低于野生型和nNOS-/-小鼠。经直肠而非静脉给予L-精氨酸可降低野生型、nNOS-/-和W/W(v)小鼠的基础张力。然而，L-精氨酸和L-NAME均未影响eNOS-/-小鼠的基础张力。在体外，L-精氨酸可降低野生型和nNOS-/- IAS的基础张力，但对无黏膜的eNOS-/-或野生型IAS无此作用。野生型、eNOS-/-和W/W(v)小鼠的体内RAIR正常，但所有nNOS-/-小鼠均无此反射。nNOS-/- IAS中EFS诱导的IAS松弛也降低。因此，黏膜中的eNOS在很大程度上控制基础IAS张力，而RAIR由nNOS控制。表达c-Kit的ICC可能对RAIR并非必不可少。
