Effects of a novel guanylate cyclase inhibitor on nitric oxide‐dependent inhibitory neurotransmission in canine proximal colon

Franck, H.; Sweeney, Kathy; Sanders, Katherine; Shuttleworth, C. William

doi:10.1038/sj.bjp.0701487

Cited by 40 publications

(36 citation statements)

References 37 publications

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“…Several functional studies (Franck et al 1997;Huber et al 1998;Young et al 1996) have demonstrated that the NO effect could be blocked by 1H-(1,2,4)-oxadiazolo-(4,3-α)quinoxaline-1-one, a selective inhibitor of sGC. Thus NOmediated smooth muscle relaxation involved an activation of sGC.…”

Section: Origin and Cellular Targets Of Nitric Oxidementioning

confidence: 98%

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine

Salmhofer

Ruth

et al. 2001

Cell and Tissue Research

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The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic transmitter mechanism in the enteric nervous system. Our aim was to localize the enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small intestine by indirect immunofluorescence. nNOS staining was found in neurons of the myenteric plexus and in varicose nerve fibers mainly in the circular muscle layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them. sGC was found in flattened cells surrounding myenteric ganglia (periganglionic cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in cells perivascularly scattered throughout the circular muscle layer. cGK-I immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less intensively in the outer circular layer. Weak cGK-I staining occurred in nerve cells within the myenteric and submucosal plexus. Conclusively the key enzymes of the NO signaling pathway are differentially distributed: Occurrence of nNOS exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC suggest a sequence of neuronal NO release, activation of ICC, and consecutive smooth muscle relaxation. ICC of the DMP seem to be the primary targets for neurally released NO.

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Section: Origin and Cellular Targets Of Nitric Oxidementioning

confidence: 98%

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine

Salmhofer

Ruth

et al. 2001

Cell and Tissue Research

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“…NO relaxes smooth muscle cells in vascular (28) and visceral (29) tissues, and much of the relaxation response is mediated via cGMP-dependent mechanisms (30,31). A portion of NO-dependent relaxation is due to hyperpolarization and/or reduced excitability that is due to activation of K ϩ channels.…”

Section: Discussionmentioning

confidence: 99%

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

Koh

Monaghan

Sergeant

et al. 2001

Journal of Biological Chemistry

126

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Potassium channels activated by membrane stretch may contribute to maintenance of relaxation of smooth muscle cells in visceral hollow organs. Previous work has identified K ؉ channels in murine colon that are activated by stretch and further regulated by NO-dependent mechanisms. We have screened murine gastrointestinal, vascular, bladder, and uterine smooth muscles for the expression of TREK and TRAAK mRNA. Although TREK-1 was expressed in many of these smooth muscles, TREK-2 was expressed only in murine antrum and pulmonary artery. TRAAK was not expressed in any smooth muscle cells tested. Whole cell currents from TREK-1 expressed in mammalian COS cells were activated by stretch, and single channel recordings showed that the stretch-dependent conductance was due to 90 pS channels. Sodium nitroprusside

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“…NO elicits hyperpolarization and relaxation responses in GI muscles, and these responses depend upon generation of cGMP and cGMP dependent protein kinase. 199,200,220 The proteins that mediate membrane hyperpolarization are debated, and some investigators have viewed the hyperpolarization response to be due to activation of a K + conductance [231][232][233] while others have suggested the response is due to suppression of an inward current due either to a non-selective cation conductance 206 or a chloride conductance. 234 Resolution of these questions and determining which of the cells in the SIP syncytium express the specific types of ion channels responsible for responses to NO will require additional experimentation.…”

Section: Evidence Opposing a Role For Interstitial Cells Of Cajal In mentioning

confidence: 99%

“…62,127,[191][192][193][194][195][196][197] Numerous studies have shown responses to NO in the GI tract depend upon the production of cyclic GMP (cGMP) by soluble guanylate cyclase. [198][199][200] Guanylate cyclase is a heterodimer comprised of 2 subunits, α and β. Using immunohistochemistry Iino et al 182,201 showed that both subunits are strongly expressed in ICC but not resolved in smooth muscle.…”

Section: Functional Evidence Demonstrating the Importance Of Interstimentioning

confidence: 99%

The Significance of Interstitial Cells in Neurogastroenterology

Blair¹,

Rhee²,

Sanders³

et al. 2014

J Neurogastroenterol Motil

116

111

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Smooth muscle layers of the gastrointestinal tract consist of a heterogeneous population of cells that include enteric neurons, several classes of interstitial cells of mesenchymal origin, a variety of immune cells and smooth muscle cells (SMCs). Over the last number of years the complexity of the interactions between these cell types has begun to emerge. For example, interstitial cells, consisting of both interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells generate pacemaker activity throughout the gastrointestinal (GI) tract and also transduce enteric motor nerve signals and mechanosensitivity to adjacent SMCs. ICC and PDGFRα + cells are electrically coupled to SMCs possibly via gap junctions forming a multicellular functional syncytium termed the SIP syncytium. Cells that make up the SIP syncytium are highly specialized containing unique receptors, ion channels and intracellular signaling pathways that regulate the excitability of GI muscles. The unique role of these cells in coordinating GI motility is evident by the altered motility patterns in animal models where interstitial cell networks are disrupted. Although considerable advances have been made in recent years on our understanding of the roles of these cells within the SIP syncytium, the full physiological functions of these cells and the consequences of their disruption in GI muscles have not been clearly defined. This review gives a synopsis of the history of interstitial cell discovery and highlights recent advances in structural, molecular expression and functional roles of these cells in the GI tract.

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Effects of a novel guanylate cyclase inhibitor on nitric oxide‐dependent inhibitory neurotransmission in canine proximal colon

Cited by 40 publications

References 37 publications

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine

Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling pathway of rat small intestine

TREK-1 Regulation by Nitric Oxide and cGMP-dependent Protein Kinase

The Significance of Interstitial Cells in Neurogastroenterology

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