In guinea-pig ileum (GPI), the chemotactic peptide N-formyl-Met-Leu-Phe-OH (fMLF) possesses spasmogenic properties through the activation of formyl peptide receptors (FPRs). Despite this, the mediators involved remain to be elucidated. fMLF (1 nM-1 mu M) induced a dose-dependent contraction of GPI (EC(50) = 24 nM), that is blocked by pre-treatment with the FPRs antagonist Boc(2). The pre-treatment with tetrodotoxin (TTX) atropine or with SR140333 reduced the fMLF-induced contraction, whereas with hexamethonium, MEN10627, SB222200, mepyramine, cimetidine, thioperamide or methysergide did not produce any effect. With DuP697 pre-treatment, but not with piroxicam, reduced the fMLF-induced contraction. After stimulation with 24 nM fMLF, a strong increase in the PGE(2) levels was observed. Finally, the concomitant blocking of the NK(1) receptor, the muscarinic receptors and COX-2 abolished the GPI contractions induced by fMLF. fMLF induced a concentration-dependent contraction of guinea-pig jejunum (EC(50) = 11 nM), proximal colon (EC(50) = 3.5 nM) and distal colon (EC(50) = 2.2 nM), with a time-course similar to that observed in GPI. In these preparations as well, the co-administration of atropine, SR140333 and DuP697 abolished the contractions induced by fMLF. Intraperitoneal injection of fMLF (0.1 or 1 mu mol/kg) enhanced the gastrointestinal motility in mice, abolished by the co-administration of atropine, SR140333 and DuP697. In conclusion, we showed that fMLF exerts spasmogenic actions on guinea-pig intestine both in vitro and in vivo through the release of acetylcholine and substance P from myenteric motorneurons and through prostanoids, probably from the inflammatory cells of the enteric immune system. (C) 2010 Elsevier Inc. All rights reserved.

Guinea pig ileum motility stimulation elicited by N-formyl-Met-Leu-Phe (fMLF) involves neurotransmitters and prostanoids / Mariantonella, Colucci; Marica, Mastriota; Francesco, Maione; Amalia Di, Giannuario; Nicola, Mascolo; Palmery, Maura; Cinzia, Severini; Mauro, Perretti; Stefano, Pieretti. - In: PEPTIDES. - ISSN 0196-9781. - STAMPA. - 32:2(2011), pp. 266-271. [10.1016/j.peptides.2010.11.019]

Guinea pig ileum motility stimulation elicited by N-formyl-Met-Leu-Phe (fMLF) involves neurotransmitters and prostanoids

PALMERY, Maura;
2011

Abstract

In guinea-pig ileum (GPI), the chemotactic peptide N-formyl-Met-Leu-Phe-OH (fMLF) possesses spasmogenic properties through the activation of formyl peptide receptors (FPRs). Despite this, the mediators involved remain to be elucidated. fMLF (1 nM-1 mu M) induced a dose-dependent contraction of GPI (EC(50) = 24 nM), that is blocked by pre-treatment with the FPRs antagonist Boc(2). The pre-treatment with tetrodotoxin (TTX) atropine or with SR140333 reduced the fMLF-induced contraction, whereas with hexamethonium, MEN10627, SB222200, mepyramine, cimetidine, thioperamide or methysergide did not produce any effect. With DuP697 pre-treatment, but not with piroxicam, reduced the fMLF-induced contraction. After stimulation with 24 nM fMLF, a strong increase in the PGE(2) levels was observed. Finally, the concomitant blocking of the NK(1) receptor, the muscarinic receptors and COX-2 abolished the GPI contractions induced by fMLF. fMLF induced a concentration-dependent contraction of guinea-pig jejunum (EC(50) = 11 nM), proximal colon (EC(50) = 3.5 nM) and distal colon (EC(50) = 2.2 nM), with a time-course similar to that observed in GPI. In these preparations as well, the co-administration of atropine, SR140333 and DuP697 abolished the contractions induced by fMLF. Intraperitoneal injection of fMLF (0.1 or 1 mu mol/kg) enhanced the gastrointestinal motility in mice, abolished by the co-administration of atropine, SR140333 and DuP697. In conclusion, we showed that fMLF exerts spasmogenic actions on guinea-pig intestine both in vitro and in vivo through the release of acetylcholine and substance P from myenteric motorneurons and through prostanoids, probably from the inflammatory cells of the enteric immune system. (C) 2010 Elsevier Inc. All rights reserved.
2011
fmlf; formyl peptide receptors; fpr; gastrointestinal transit; gpi; guinea-pig intestine
01 Pubblicazione su rivista::01a Articolo in rivista
Guinea pig ileum motility stimulation elicited by N-formyl-Met-Leu-Phe (fMLF) involves neurotransmitters and prostanoids / Mariantonella, Colucci; Marica, Mastriota; Francesco, Maione; Amalia Di, Giannuario; Nicola, Mascolo; Palmery, Maura; Cinzia, Severini; Mauro, Perretti; Stefano, Pieretti. - In: PEPTIDES. - ISSN 0196-9781. - STAMPA. - 32:2(2011), pp. 266-271. [10.1016/j.peptides.2010.11.019]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/376118
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