Involvement of nitric oxide and tachykinins in the effects induced by protease‐activated receptors in rat colon longitudinal muscle

Abstract

1 The aim of the present study was to verify a possible involvement of nitric oxide (NO) and of tachykinins in the contractile and relaxant effects caused by the activation of protease-activated receptor (PAR)-1 and PAR-2 in the longitudinal muscle of rat colon. 2 Mechanical responses to the PAR-1 activating peptides, SFLLRN-NH 2 (10 nM -10 mM) and TFLLR-NH 2 (10 nM -10 mM), and to the PAR-2-activating peptide, SLIGRL-NH 2 (10 nM -10 mM), were examined in vitro in the absence and in the presence of different antagonists. The contractile responses to PAR-1 and PAR-2 activation were concentration-dependently attenuated by SR140333 (0.1 -1 mM), NK 1 receptor antagonist, or by SR48968 (0.1 -1 mM), NK 2 receptor antagonist. The combined pretreatment with SR140333 (1 mM) and SR48968 (1 mM) produced additive suppressive effects on the contractile responses to PAR activation. Pretreatment of the preparation with capsaicin (10 mM) markedly reduced the contractions evoked by SFLLRN-NH 2 , TFLLR-NH 2 and SLIGRL-NH 2 , while o-conotoxin GVIA (0.2 mM) had no effect. 5 The present results suggest that in rat colonic longitudinal muscle, PAR-1 and PAR-2 activation can evoke (i) relaxation through the production of NO or (ii) contraction through the release of tachykinins, likely, from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat

“…POSTINFECTIOUS PAR-2-ASSOCIATED INTESTINAL DYSFUNCTION the participation of specific neurotransmitters in the different phases of PAR-2-mediated responses, as previously described in the rat colon (25). Further studies are needed to characterize the underlying mechanisms generating PAR-2-mediated biphasic secretory and motor responses in the jejunum.…”

“…Therefore, it is feasible that PAR-2-mediated increased motility and luminal secretion would contribute to a "protective" response, controlling penetration and interaction of luminal antigens with the epithelium and bacterial overgrowth in physiological conditions (3,27). In addition, these PAR-2-mediated defensive responses are apparently induced by direct effects on the epithelium and the muscle, as the modulation of secretion and motility by SLIGRL-NH 2 was TTX independent (25,26,47). Nevertheless, we cannot rule out …”

Acute Allergic Skin Reactions and Intestinal Contractility Changes in Mice Orally Sensitized against Casein or Whey

“…In addition, local mast cell degranulation may have induced motility changes [11]. Mule et al [29, 50] have shown that activation of protease-activated receptors (PAR) can cause colon smooth muscle relaxation as well as contraction. PAR agonists such as mast cell-derived tryptase may have caused PAR activation in both casein- and whey-sensitized mice.…”

Proinflammatory Cytokines Suppress the Expression Level of Protease-Activated Receptor-2 through the Induction of iNOS in Rat Colon

“…5). In intestinal smooth muscle, PAR-2 agonist induces relaxation by the activation of small conductance Ca 2+ -activated K + -channel opened with the influx of extracellular Ca 2+ through L-type voltage-dependent channels [19,26], by the production of NO [18] or by the activation of enteric inhibitory neurons [16]. Under inflammatory conditions, the activity of smooth muscle L-type Ca 2+ channels is suppressed [1,13,28], the cGMP-relaxation pathway is damaged [31] and non-adrenergic non-cholinergic nerves are impaired [17].…”