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.

Carbon monoxide mediates vasoactive intestinal polypeptide-associated nonadrenergic/noncholinergic neurotransmission

“…1). We detect strong immunoreactivity of HO2 and VIP in neurons of the myenteric plexus innervating the IAS, similar to what has been shown in studies (11,29). In Ϸ50% of these neurons, we detect colocalization of VIP and HO2, although they also occur in distinct neurons (Fig.…”

“…In other studies, we have observed HO2 and nNOS predominantly in the myenteric plexus throughout the gastrointestinal pathway (13,41). The similarity of VIP, nNOS, and HO2 localizations in mouse IAS to localizations throughout the gastrointestinal tract (11)(12)(13) implies that VIP-NANC transmission at other sites involves similar mechanisms as are involved in IAS. Our findings can be explained by VIP acting on HO2 in neurons that contain both of these substances, i.e., in an autocrine fashion (Fig.…”

“…Neuronal NO synthase (nNOS) and heme oxygenase 2 (HO2), the biosynthetic enzyme for CO, are localized to the myenteric plexus of gastrointestinal neurons (9,10). Moreover, in many instances, nNOS and HO2 are colocalized, suggesting that they may function as cotransmitters (11)(12)(13)(14). Inhibitors of nNOS and HO2 block NANC transmission (15)(16)(17).…”

Preventive Effect of <i>Lactobacillus fermentum</i> Zhao on Activated Carbon-Induced Constipation in Mice

“…Therefore, in order to study whether lactic acid bacteria can pass through the stomach and intestine to colonize in intestinal tract, we built an external virtual model of the intestinal tract, and screened lactic acid bacteria capable of growing in that model. Their potential probiotic functions can be identified by measuring their acid-resistance, cholate tolerance and hydrophobic property (11). LF-Zhao showed better acidresistance, cholate tolerance and hydrophobic property than LB, and these high qualities could result in functional effects of LF-Zhao for use in humans.…”

“…Bisacodyl is a laxative drug that stimulates intestinal peristalsis and acts directly on the colon to produce bowel movement. It is typically prescribed for the relief of constipation and for the management of neurogenic bowel dysfunction, as well as for bowel preparation prior to medical examinations (9)(10)(11).…”