title: Heme oxygenase-2 distribution in anorectum: colocalization with neuronal nitric oxide synthase.
abstract: Recent investigations have suggested carbon monoxide (CO) as a putative messenger molecule. Although several studies have implicated the heme oxygenase (HO) pathway, responsible for the endogenous production of CO, in the neuromodulatory control of the internal anal sphincter (IAS), its exact role is not known. Nitric oxide, produced by neuronal nitric oxide synthase (nNOS) of myenteric neurons, is an important inhibitory neural messenger molecule mediating nonadrenergic noncholinergic (NANC) relaxation of the IAS. The present studies were undertaken to investigate in detail the presence and coexistence of heme oxygenase-2 (HO-2) with nNOS in the opossum anorectum. In perfusion-fixed, frozen-sectioned tissue, HO-2 immunoreactive (IR) and nNOS IR nerves were identified using immunocytochemistry. Ganglia containing HO-2 IR neuronal cell bodies were present in the myenteric and submucosal plexuses throughout the entire anorectum. Colocalization of HO-2 IR and nNOS IR was nearly 100% in the IAS and decreased proximally from the anal verge. In the rectum, colocalization of HO-2 IR and nNOS IR was approximately 70%. Additional confocal microscopy studies using c-Kit staining demonstrated the localization of HO-2 IR and nNOS IR in interstitial cells of Cajal (ICC) of the anorectum. From the high rate of colocalization of HO-2 IR and nNOS IR in the IAS as well as the localization of HO-2 IR and nNOS IR in ICC in conjunction with earlier studies of the HO pathway, we speculate an interaction between HO and NOS pathways in the NANC inhibitory neurotransmission of the IAS and rectum.
authors.affiliation: Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: R
authors.initials: R
authors.lastname: Battish
authors.forename: G Y
authors.initials: GY
authors.lastname: Cao
authors.forename: R B
authors.initials: RB
authors.lastname: Lynn
authors.forename: S
authors.initials: S
authors.lastname: Chakder
authors.forename: S
authors.initials: S
authors.lastname: Rattan
mesh_terms: D001003:Anal Canal / Q000201:enzymology* / Q000294:innervation; D000818:Animals; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009893:Opossums; D012007:Rectum / Q000201:enzymology* / Q000294:innervation; D013368:Submucous Plexus / Q000201:enzymology; D014018:Tissue Distribution
chemical_list: D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2