Receptor-activating peptides for PAR-1 and PAR-2 relax rat gastric artery via multiple mechanisms.

Receptor-activating peptides for protease-activated receptors (PARs) 1 or 2 enhance gastric mucosal blood flow (GMBF) and protect against gastric mucosal injury in rats. We thus examined and characterized the effects of PAR-1 and PAR-2 agonists on the isometric tension in isolated rat gastric artery. The agonists for PAR-2 or PAR-1 produced vasodilation in the endothelium-intact arterial rings, which was abolished by removal of the endothelium.

Activation of trigeminal nociceptive neurons by parotid PAR-2 activation in rats.

To clarify involvement of protease-activated receptor-2 (PAR-2) in parotid pain, we examined whether PAR-2 activation in the parotid gland could activate trigeminal nociceptive neurons in anesthetized rats, by analyzing immunoreactive Fos as a nociceptive marker. Either the PAR-2 agonist SLIGRL-NH2 or capsaicin, injected into the parotid duct, caused expression of Fos in the trigeminal subnucleus caudalis, although the PAR-2-inactive reversed peptide had no such effect. The Fos expression caused by PAR-2 activation was inhibited by ablation of capsaicin-sensitive sensory neurons.

Proteinase-activated receptor-2-mediated relaxation in mouse tracheal and bronchial smooth muscle: signal transduction mechanisms and distinct agonist sensitivity.

We characterized the tracheal and bronchial relaxation caused by proteinase-activated receptor-2 (PAR-2) activation in ddY mice and/or in wild-type and PAR-2-knockout mice of C57BL/6 background. Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-NH(2)) and Thr-Phe-Leu-Leu-Arg-amide, PAR-2- and PAR-1-activating peptides, respectively, caused relaxation in the isolated ddY mouse trachea and main bronchus. The relaxation was abolished by specific inhibitors of cyclooxygenase (COX)-1, COX-2, mitogen-activated protein kinase kinase (MEK), and p38 MAP kinase.

Modulation of capsaicin-evoked visceral pain and referred hyperalgesia by protease-activated receptors 1 and 2.

Protease-activated receptors (PARs) 1 and 2 are expressed in capsaicin-sensitive sensory neurons, being anti- and pro-nociceptive, respectively. Given the possible cross talk between PAR-2 and capsaicin receptors, we investigated if PAR-2 activation could facilitate capsaicin-evoked visceral pain and referred hyperalgesia in the mouse and also examined the effect of PAR-1 activation in this model. Intracolonic (i.

Distinct roles for protease-activated receptors 1 and 2 in vasomotor modulation in rat superior mesenteric artery.

Objective: Protease-activated receptors (PARs) 1 and 2 are expressed in various blood vessels including rat aorta, modulating vascular tone. We investigated the roles of PAR-1 and PAR-2 in vasomotor modulation in rat superior mesenteric artery.

Methods And Results: Effects of the PAR-2-activating peptide Ser-Leu-Ile-Gly-Arg-Leu-amide (SLIGRL-amide) and the PAR-1-activating peptide Thr-Phe-Leu-Leu-Arg-amide (TFLLR-amide) on isometric tension were examined in isolated rat superior mesenteric artery or aorta.

Potent and metabolically stable agonists for protease-activated receptor-2: evaluation of activity in multiple assay systems in vitro and in vivo.

To develop potent and metabolically stable agonists for protease-activated receptor-2 (PAR-2), we prepared 2-furoylated (2f) derivatives of native PAR-2-activating peptides, 2f-LIGKV-OH, 2f-LIGRL-OH, 2f-LIGKV-NH(2), and 2f-LIGRL-NH(2), and systematically evaluated their activity in PAR-2-responsive cell lines and tissues. In both HCT-15 cells and NCTC2544 cells overexpressing PAR-2, all furoylated peptides increased cytosolic Ca(2+) levels with a greater potency than the corresponding native peptides, although a similar maximum response was recorded. The absolute potency of each peptide was greater in NCTC2544, possibly due to a higher level of receptor expression.

The PAR-1-activating peptide facilitates pepsinogen secretion in rats.

Protease-activated receptor-2 (PAR-2) is abundantly expressed in gastric mucosal chief cells, facilitating pepsinogen secretion. In the present study, we investigated whether PAR-1, a thrombin receptor, could modulate pepsinogen secretion in rats. The PAR-1-activating peptide TFLLR-NH(2) as well as the PAR-2-activating peptide SLIGRL-NH(2), administered i.

A protective role of protease-activated receptor 1 in rat gastric mucosa.

Background And Aims: On activation, protease-activated receptor (PAR)-2 modulates multiple gastric functions and exerts mucosal protection via activation of sensory neurons. The role of PAR-1, a thrombin receptor, in the stomach remains unknown. We thus examined if the PAR-1 agonist could protect against gastric mucosal injury in rats.

Involvement of EDHF in the hypotension and increased gastric mucosal blood flow caused by PAR-2 activation in rats.

1. Agonists for protease-activated receptor-2 (PAR-2) cause hypotension and an increase in gastric mucosal blood flow (GMBF) in vivo. We thus studied the mechanisms underlying the circulatory modulation by PAR-2 activation in vivo, especially with respect to involvement of endothelium-derived hyperpolarizing factor (EDHF).

[Pain information pathways from the periphery to the cerebral cortex].

A recent PET study revealed that the first and second somatosensory cortices (SI, SII), and the anterior cingulate cortex are activated by painful peripheral stimulation in humans. It has become clear that painful signals (nociceptive information) evoked at the periphery are transmitted via various circuits to the multiple cerebral cortices where pain signals are processed and perceived. Human or clinical pain is not merely a modality of somatic sensation, but associated with the affect that accompanies sensation.

[PAR (protease-activated receptor) as a novel target for development of gastric mucosal cytoprotective drugs].

Protease-activated receptor-2 (PAR-2), a G protein-coupled seven trans-membrane domain receptor, is distributed throughout the gastrointestinal tract, modulating various functions. In gastric mucosa, PAR-2 present in sensory neurons, upon activation, triggers mucus secretion by stimulating release of CGRP and tachykinins, resulting mucosal cytoprotection. PAR-2 activation also suppresses acid secretion and increase mucosal blood flow, contributing to the protective mechanisms.

Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland: Immunolocalization and involvement of nitric oxide in the evoked amylase secretion.

Protease-activated receptor-2, a G protein-coupled receptor activated by serine proteases such as trypsin, tryptase and coagulation factors VIIa and Xa, modulates pancreatic and salivary exocrine secretion. In the present study, we examined the distribution of PAR-2 in the pancreas and parotid gland, and characterized the PAR-2-mediated secretion of amylase by these tissues in vivo. Immunohistochemical analyses using the polyclonal antibody against rat PAR-2 clearly showed abundant expression of PAR-2 in rat pancreatic and parotid acini.

Role of N-methyl-D-aspartate receptors and the nitric oxide pathway in nociception/hyperalgesia elicited by protease-activated receptor-2 activation in mice and rats.

Activation of the peripheral protease-activated receptor-2 (PAR-2) triggers nociceptive behaviour and thermal hyperalgesia in rats. The present study created a novel mouse model for PAR-2-triggered nociception, and then examined the roles of NMDA receptors and the nitric oxide (NO) pathway in nociceptive processing by PAR-2. Intraplantar administration of the PAR-2 agonist SLIGRL-NH(2) elicited nociceptive responses in mice, an effect being more specific in mast cell-depleted mice.

The PAR-1-activating peptide attenuates carrageenan-induced hyperalgesia in rats.

We examined if thrombin or a receptor-activating peptide for protease-activated receptor-1 (PAR-1), a thrombin receptor, could modulate nociception at peripheral levels. Intraplantar administration of PAR-1 activators, thrombin or TFLLR-NH(2), but not its inactive control FTLLR-NH(2) or a PAR-2 activator SLIGRL-NH(2), significantly attenuated the hyperalgesia in rats treated with carrageenan, although they had no effect on nociception in naïve rats. The thrombin-PAR-1 system might thus act to attenuate nociception during inflammatory hyperalgesia.

Capsazepine inhibits thermal hyperalgesia but not nociception triggered by protease-activated receptor-2 in rats.

Protease-activated receptor-2 (PAR-2), expressed in sensory neurons, triggers thermal hyperalgesia, nociceptive behavior and spinal Fos expression in rats. In the present study, we examined if the nociceptive processing by PAR-2 is mediated by trans-activation of capsaicin receptors. The thermal hyperalgesia following an intraplantar (i.

Suppression by protease-activated receptor-2 activation of gastric acid secretion in rats.

Activation of protease-activated receptor-2 (PAR-2), a receptor activated by trypsin/tryptase, induces neurally mediated gastric mucus secretion accompanied by mucosal cytoprotection. In the present study, we investigated whether PAR-2 could modulate gastric acid secretion in rats. Messenger RNAs for PAR-2 and PAR-1 were detected in the gastric mucosa and smooth muscle.

Effects of somatosensory cortical stimulation on expression of c-Fos in rat medullary dorsal horn in response to formalin-induced noxious stimulation.

We examined the effects of epidural electrical stimulation of primary (SI) and secondary (SII) somatosensory cortex on expression of c-Fos protein in rat medullary dorsal horn neurons (Vc; trigeminal nucleus caudalis) in response to formalin-induced noxious stimulation. Epidural electrical stimulation (single pulse, 0.2 msec duration at 10 Hz) was applied to the left facial region SI or SII at three different stimulus intensities, 0.

Capsazepine partially inhibits neurally mediated gastric mucus secretion following activation of protease-activated receptor 2.

1. Protease-activated receptor 2 (PAR2), present in capsaicin-sensitive sensory neurons, induces gastric mucus secretion and mucosal cytoprotection. 2.

Specific expression of spinal Fos after PAR-2 stimulation in mast cell-depleted rats.

Protease-activated receptor-2 (PAR-2) in the sensory neurons may be involved in nociceptive processing. We attempted to detect and characterize specific expression of spinal Fos, a marker of nociception, in mast cell-depleted rats. Intraplantar (i.

Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa: immunolocalization and facilitation of pepsin/pepsinogen secretion.

1. Agonists of protease-activated receptor-2 (PAR-2) trigger neurally mediated mucus secretion accompanied by mucosal cytoprotection in the stomach. The present study immunolocalized PAR-2 in the rat gastric mucosa and examined if PAR-2 could modulate pepsin/pepsinogen secretion in rats.