Nociceptin/OrphaninFQ (N/OFQ) and Nociceptin Orphan Peptide (NOP) receptors represent an endogenous system modulating gastrointestinal functions and inflammation. The role of N/OFQergic system on some inflammatory variables in a rat model of colitis induced by intracolonic (IC) instillation of TNBS (2,4,6 trinitrobenzensulfonic acid) (60 mg/kg, IC) has been investigated. Male Wistar rats received two intraperitoneal (IP) injections per day of N/OFQ (0.02-0.2-2-20 nmol/kg) or NOP receptor selective antagonist, UFP-101 (1-3-10 nmol/kg), or saline for three days after induction of colitis. Four days after TNBS, animals were sacrificed and colonic histological damage, myeloperoxidase (MPO) activity, cytokine levels were evaluated. N/OFQ plasmatic concentration was assessed by radioimmunoassay. TNBS increased all the inflammatory variables considered in comparison with control animals. In colitic rats, N/OFQ at 0.02 and 0.2 nmol/kg improved microscopic damage and MPO activity, and decreased colonic IL-1 level in comparison with TNBS group, whereas at the highest dose (20 nmol/kg) worsened colitis. UFP-101 at a dose of 1 nmol/kg, without intrinsic activity, antagonized the protective effect of N/OFQ (0.2 nmol/kg) on colitis. At the doses of 3 and 10 nmol/kg, UFP-101 worsened colitis revealing an antiinflammatory role of the endogenous N/OFQergic system. No differences in N/OFQ plasmatic levels have been observed between controls and TNBS-treated rats. In contrast, treatment with UFP-101 at the doses (3 and 10 nmol/kg) that worsen colitis significantly reduced N/OFQ concentration in the plasma of colitic rats. In conclusion: 1) the anti-inflammatory action of peripheral low doses of N/OFQ (1000-10000 fold lower than those that worsen colitis) is mediated by the activation of peripheral NOP receptors; 2) the endogenous N/OFQergic system has a protective role in the control of inflammation in experimental colitis in rats, and it could be considered an interesting target for the treatment of pathological inflammatory conditions of the gastrointestinal tract.
Immunomodulatory role of nociceptin/orphanin FQ - NOP receptor system in a rat model of experimental colitis / Petrella, Carla; Giuli, Chiara; H., Eutamene; C., Cartier; M., Leveque; A., Bedini; S., Spampinato; L., Bueno; V., Theodorou; Broccardo, Maria; Improta, Giovanna; S., Agostini. - (2012). (Intervento presentato al convegno Join International Neurogastroenterology and Motility Meeting tenutosi a Bologna nel 6-8 Spetember 2012).
Immunomodulatory role of nociceptin/orphanin FQ - NOP receptor system in a rat model of experimental colitis
PETRELLA, CARLA;GIULI, CHIARA;BROCCARDO, Maria;IMPROTA, Giovanna;
2012
Abstract
Nociceptin/OrphaninFQ (N/OFQ) and Nociceptin Orphan Peptide (NOP) receptors represent an endogenous system modulating gastrointestinal functions and inflammation. The role of N/OFQergic system on some inflammatory variables in a rat model of colitis induced by intracolonic (IC) instillation of TNBS (2,4,6 trinitrobenzensulfonic acid) (60 mg/kg, IC) has been investigated. Male Wistar rats received two intraperitoneal (IP) injections per day of N/OFQ (0.02-0.2-2-20 nmol/kg) or NOP receptor selective antagonist, UFP-101 (1-3-10 nmol/kg), or saline for three days after induction of colitis. Four days after TNBS, animals were sacrificed and colonic histological damage, myeloperoxidase (MPO) activity, cytokine levels were evaluated. N/OFQ plasmatic concentration was assessed by radioimmunoassay. TNBS increased all the inflammatory variables considered in comparison with control animals. In colitic rats, N/OFQ at 0.02 and 0.2 nmol/kg improved microscopic damage and MPO activity, and decreased colonic IL-1 level in comparison with TNBS group, whereas at the highest dose (20 nmol/kg) worsened colitis. UFP-101 at a dose of 1 nmol/kg, without intrinsic activity, antagonized the protective effect of N/OFQ (0.2 nmol/kg) on colitis. At the doses of 3 and 10 nmol/kg, UFP-101 worsened colitis revealing an antiinflammatory role of the endogenous N/OFQergic system. No differences in N/OFQ plasmatic levels have been observed between controls and TNBS-treated rats. In contrast, treatment with UFP-101 at the doses (3 and 10 nmol/kg) that worsen colitis significantly reduced N/OFQ concentration in the plasma of colitic rats. In conclusion: 1) the anti-inflammatory action of peripheral low doses of N/OFQ (1000-10000 fold lower than those that worsen colitis) is mediated by the activation of peripheral NOP receptors; 2) the endogenous N/OFQergic system has a protective role in the control of inflammation in experimental colitis in rats, and it could be considered an interesting target for the treatment of pathological inflammatory conditions of the gastrointestinal tract.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
