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Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation.
Am J Physiol Gastrointest Liver Physiol. 2005 Aug; 289(2):G291-9.AJ

Abstract

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.

Authors+Show Affiliations

Center of Swallowing and Motility Disorders, Department of Veterans Affairs Medical Center, 1400 VFW Parkway, West Roxbury, MA 02132, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15845873

Citation

Terauchi, Akiko, et al. "Distinct Roles of Nitric Oxide Synthases and Interstitial Cells of Cajal in Rectoanal Relaxation." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 289, no. 2, 2005, pp. G291-9.
Terauchi A, Kobayashi D, Mashimo H. Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation. Am J Physiol Gastrointest Liver Physiol. 2005;289(2):G291-9.
Terauchi, A., Kobayashi, D., & Mashimo, H. (2005). Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation. American Journal of Physiology. Gastrointestinal and Liver Physiology, 289(2), G291-9.
Terauchi A, Kobayashi D, Mashimo H. Distinct Roles of Nitric Oxide Synthases and Interstitial Cells of Cajal in Rectoanal Relaxation. Am J Physiol Gastrointest Liver Physiol. 2005;289(2):G291-9. PubMed PMID: 15845873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct roles of nitric oxide synthases and interstitial cells of Cajal in rectoanal relaxation. AU - Terauchi,Akiko, AU - Kobayashi,Daisuke, AU - Mashimo,Hiroshi, Y1 - 2005/04/21/ PY - 2005/4/23/pubmed PY - 2005/9/1/medline PY - 2005/4/23/entrez SP - G291 EP - 9 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 289 IS - 2 N2 - 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. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/15845873/Distinct_roles_of_nitric_oxide_synthases_and_interstitial_cells_of_Cajal_in_rectoanal_relaxation_ DB - PRIME DP - Unbound Medicine ER -