Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent pathway

Liu, H.; Miller, David V.; Lourenssen, Sandra; Wells, Ron W.; Blennerhassett, Michael G.; Paterson, William G.

doi:10.1111/j.1365-2982.2009.01394.x

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…In fact, repeated acid infusion into the esophagus both sensitizes and potentiates longitudinal muscle contraction [28]. In response to acid infusion, mast cells located in the submucosa release a number of chemicals including histamine, serotonin, and trypsin [29,30]. One study found that these chemicals act on the capsaicin-sensitive nerve endings (extrinsic afferents) to release neurokinins and substance P that stimulate tachykinin receptors on the longitudinal muscles.…”

Section: Pharmacology Of the Esophageal Longitudinal Musclementioning

confidence: 99%

Longitudinal muscle of the esophagus

Mittal¹

2013

Current Opinion in Gastroenterology

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Section: Pharmacology Of the Esophageal Longitudinal Musclementioning

confidence: 99%

Longitudinal muscle of the esophagus

Mittal¹

2013

Current Opinion in Gastroenterology

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“…In these studies, the biphasic responses consisted of an initial relaxation followed by a contraction and the relaxant effects were observed at lower concentrations than those required for the contractile effects. In one study (Liu et al, 2010), the contractile effect was partly dependent on the release of contractile neurotransmitters from capsaicin-sensitive nerves, while in another study (Huang, 2007), it was shown to be resistant to tetrodotoxin. The myogenic biphasic regulation with initial contraction followed by relaxation thus appears to be unique to the LES.…”

Section: Discussionmentioning

confidence: 96%

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

Tanaka

Ihara

Hirano

et al. 2015

European Journal of Pharmacology

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The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300nM) induced a transient contraction. At concentrations of 1μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1μM)-induced contractions were partially inhibited by pretreatment with 10μM Y-27632. In addition, trypsin (10μM)-induced relaxation was partially inhibited by pretreatment with 10μM Y-27632, 10μM PD98059 or 10μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K(+) concentration to 40mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10μM glibenclamide or 1μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.

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“…In fact, repeated acid infusion into the esophagus sensitizes and potentiates longitudinal muscle contraction 29. In response to acid infusion, mast cells located in the submucosa release number of chemicals, histamine, serotonin and trypsine 30,31. These chemicals act on the capsaicin sensitive nerve endings (extrinsic afferent) to release neurokinins and substance P to stimulate tachykinin receptors on the longitudinal muscles.…”

Section: Patterns Of Longitudinal Muscle Contraction In Health and Itmentioning

confidence: 99%

Longitudinal Muscle Dysfunction in Achalasia Esophagus and Its Relevance

Mittal¹,

Hong²,

Bhargava³

2013

J Neurogastroenterol Motil

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Muscularis propria of the esophagus is organized into circular and longitudinal muscle layers. Goal of this review is to summarize the role of longitudinal muscle in physiology and pathophysiology of esophageal sensory and motor function. Simultaneous manometry and ultrasound imaging that measure circular and longitudinal muscle contraction respectively reveal that during peristalsis 2 layers of the esophagus contract in perfect synchrony. On the other hand, during transient relaxation of the lower esophageal sphincter (LES), longitudinal muscle contracts independently of circular muscle. Recent studies provide novel insights, i.e., longitudinal muscle contraction of the esophagus induces LES relaxation and possibly descending relaxation of the esophagus. In achalasia esophagus and other motility disorders there is discoordination between the 2 muscle layers. Longitudinal muscle contraction patterns are different in the recently described three types of achalasia identified by high-resolution manometry. Robust contraction of the longitudinal muscle in type II achalasia causes pan-esophageal pressurization and is the mechanism of whatever little esophageal emptying that take place in the absence of peristalsis and impaired LES relaxation. It may be that preserved longitudinal muscle contraction is also the reason for superior outcome to medical/surgical therapy in type II achalasia esophagus. Prolonged contractions of longitudinal muscles of the esophagus is a possible mechanism of heartburn and "angina like" pain seen in esophageal motility disorders and possibly achalasia esophagus. Novel techniques to record longitudinal muscle contraction are on the horizon. Neuro-pharmacologic control of circular and longitudinal muscles is different, which provides an important opportunity for the development of novel pharmacological therapies to treat sensory and motor disorders of the esophagus.

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Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent pathway

Cited by 10 publications

References 23 publications

Longitudinal muscle of the esophagus

Longitudinal muscle of the esophagus

Trypsin-induced biphasic regulation of tone in the porcine lower esophageal sphincter

Longitudinal Muscle Dysfunction in Achalasia Esophagus and Its Relevance

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