A Comparative Study of Structure and Function of the Longitudinal Muscle of the Anal Canal and the Internal Anal Sphincter in Pigs

Abstract

The motility of the internal anal sphincter includes myogenic tone, relaxation mediated by nitric oxide and purinergic P2Y1 receptors, and contraction mediated by cholinergic motor neurons and sympathetic fibers. The motility of the longitudinal muscle is limited to a contraction mediated by cholinergic neurons, suggesting that longitudinal muscle contracts during relaxation of the internal sphincter, shortening the anal canal. Nicotinic, muscarinic, and serotoninergic receptors might be therapeutic targets for anal motor disorders.

Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter

“…Vasoactive intestinal polypeptide has been reported to contribute to inhibitory NMT in the internal anal sphincter (IAS) of various animal species, including humans (Burleigh et al 1979;Biancani et al 1985;Nurko & Rattan, 1988;Rattan et al 2005;Raghavan et al 2011), along with nitrergic and purineric NMT (Burleigh, 1992;O'Kelly et al 1993;Rae & Muir, 1996;De Luca et al 1999;Jones et al 2003;Opazo et al 2009Opazo et al , 2011. However, until recently it has been difficult specifically to isolate VIP-ergic NMT, because of the overlapping effects of nitrergic and purinergic NMT and the absence of effective blockers of these pathways.…”

“…Likewise, although ATP was the first of the 'non-adrenergic, non-cholinergic' substances proposed as an inhibitory neurotransmitter in the GI tract (for review see Burnstock, 1972), studies of purinergic NMT have historically been complicated by the wide range of purinergic receptor subtypes possibly involved and the absence of selective and efficacious antagonists of these receptors and their pathways. Recently, studies demonstrating the important role of P2Y 1 receptors in purinergic NMT in the GI tract have improved the situation, because this receptor can be blocked effectively in some species with the P2Y 1 receptor antagonist MRS2179 (Gallego et al 2006;Wang et al 2007;Opazo et al 2009). However, even this antagonist is of limited utility in some animals (e.g.…”

Specific and complementary roles for nitric oxide and ATP in the inhibitory motor pathways to rat internal anal sphincter

“…The rectoanal inhibitory reflex is initiated by stimulation of rectal mechanoreceptors by rectal distension and descendent stimulation of intrinsic inhibitory motor neurons (MNs) in the internal anal sphincter (IAS) 1 . In vitro studies on humans 2,3 and pigs 4,5 mainly attribute IAS relaxation to nitric oxide (NO) release. However, in species such as the rabbit, 6 rat, 7 guinea pig, 8 and opossum 9 other mediators such as ATP, vasoactive intestinal peptide (VIP), and/or CO are complementary inhibitory neurotransmitters which contribute to IAS relaxation.…”

Patterns of impaired internal anal sphincter activity in patients with anal fissure

“…Highresolution anorectal manometry showed the propagation of the USW along the IAS; in contrast, SW were always simultaneous contractions throughout the entire length of the IAS. Moreover, in in vitro studies, SW and USW in isolated human [27] and porcine [9] IAS strips were unaffected by tetrodotoxin and abolished by nifedipine, which suggests that their origin is in the IAS smooth muscle. In our study, the presence of USW was a marker of disease severity, with patients with USW having higher resting anal pressure and impairment in IAS relaxation.…”

“…Nitric oxide (NO) released after stimulation of intrinsic inhibitory motor neurons is the main inhibitory neurotransmitter causing relaxation of the IAS during the RAIR . Myogenic IAS tone mostly originates from the tonic contraction of circular smooth muscle cells and is modulated by RhoA/ROCK proteins , arachidonic acid metabolites and intrinsic myenteric neurons, which also tonically release NO.…”