Activity of Protease-Activated Receptors in the Human Submucous Plexus

Mueller, Kerstin; Michel, Klaus; Krueger, Dagmar; Demir, Ihsan Ekin; Ceyhan, Güralp O.; Zeller, Florian; Kreis, Martin E.; Schemann, Michael

doi:10.1053/j.gastro.2011.08.034

Cited by 40 publications

(65 citation statements)

References 34 publications

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“…In opposition to rodent enteric system, most neurons and glia in human submucous plexus responded to PAR 1 -AP and thrombin application, whereas activation of PAR 2 and PAR 4 generated minor responses in a limited number of neurons and glia [41]. In opposition to human, PAR 2 -AP evoked a much stronger response in guinea pig submucous neurons [41]. The same discrepancy was also observed in the myenteric plexus [42].…”

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 77%

“…The same group describes the effects of PARs activation in the human enteric nervous system in comparison to guinea pig submucous plexus. They demonstrated that stimulation of PARs by PAR-APs and by the endogenous proteases thrombin or tryptase activated neurons and glia in the human submucous plexus [41]. In opposition to rodent enteric system, most neurons and glia in human submucous plexus responded to PAR 1 -AP and thrombin application, whereas activation of PAR 2 and PAR 4 generated minor responses in a limited number of neurons and glia [41].…”

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 99%

“…They demonstrated that stimulation of PARs by PAR-APs and by the endogenous proteases thrombin or tryptase activated neurons and glia in the human submucous plexus [41]. In opposition to rodent enteric system, most neurons and glia in human submucous plexus responded to PAR 1 -AP and thrombin application, whereas activation of PAR 2 and PAR 4 generated minor responses in a limited number of neurons and glia [41]. In opposition to human, PAR 2 -AP evoked a much stronger response in guinea pig submucous neurons [41].…”

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 99%

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Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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Abstract:The protease-activated receptors (PARs) play a pivotal role in inflammatory and nociceptive processes. PARs have raised considerable interest because of their capacity to regulate numerous aspects of viscera physiology and pathophysiology. The present article summarizes research on PARs and proteases as signalling molecules in visceral pain. In particular, experiments in animal models suggest that PAR 2 is important for visceral hypersensitivity. Moreover, endogenous PAR 2 agonists seem to be released by colonic tissue of patients suffering from irritable bowel syndrome, suggesting a role for this receptor in visceral pain perception. Thus, PARs, together with proteases that activate them, represent exciting targets for therapeutic intervention on visceral pain.

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Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 77%

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 99%

Section: Implication Of Protease-activated Receptors In Visceral Painmentioning

confidence: 99%

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Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Cenac

2013

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“…In this context, it is important to realise that the contribution of PARs is different between rodent and human enteric neurons. While submucous neurons in the guinea pig have strong responses to PAR2 activation, PAR1 seems to be the dominant receptor in human submucous neurons 55. It needs to be considered that PARs are present on muscle cells, epithelial cells and immune cells as well as on neurons.…”

Section: Proteolytic Activation Of Neuronsmentioning

confidence: 99%

“…It needs to be considered that PARs are present on muscle cells, epithelial cells and immune cells as well as on neurons. For example, human tissue resident macrophages are activated by PAR2 ligands 55. Therefore, the disease relevant PAR signalling is a combination of several neuronal and non-neuronal pathways.…”

Section: Proteolytic Activation Of Neuronsmentioning

confidence: 99%

Republished: Bacterial proteases in IBD and IBS

Steck

Mueller

Schemann

et al. 2012

Postgraduate Medical Journal

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Proteases play a decisive role in health and disease. They fulfil diverse functions and have been associated with the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). The current knowledge focuses on host-derived proteases including matrix metalloproteinases, various serine proteases and cathepsins. The possible contribution of bacterial proteases has been largely ignored in the pathogenesis of IBD and IBS, although there is increasing evidence, especially demonstrated for proteases from pathogenic bacteria. The underlying mechanisms extend to proteases from commensal bacteria which may be relevant for disease susceptibility. The intestinal microbiota and its proteolytic capacity exhibit the potential to contribute to the pathogenesis of IBD and IBS. This review highlights the relevance of host- and bacteria-derived proteases and their signalling mechanisms.

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Animal Models of Disease for Future Toxicity Predictions

Morgan

Elangbam

2016

Drug Discovery Toxicology

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Activity of Protease-Activated Receptors in the Human Submucous Plexus

Cited by 40 publications

References 34 publications

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Protease-Activated Receptors as Therapeutic Targets in Visceral Pain

Republished: Bacterial proteases in IBD and IBS

Animal Models of Disease for Future Toxicity Predictions

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