Nociceptin and neurotransmitter release in the periphery

Giuliani, Sandro; Lecci, Alessandro; Maggi, Carlo Alberto

doi:10.1016/s0196-9781(00)00237-0

Cited by 37 publications

(31 citation statements)

References 54 publications

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“…In the CNS, nociceptin may be algesic and thus acting opposite to the opioid agonist. In the peripherial nervous system there is a substantial overlap of the effects produced by activation of the ORL-1 receptor and the opioid receptors [72]. The bidirectional effects of nociceptin may depend on the activation of either µ-sensitive secondary cells or κ-sensitive primary cells in the nucleus raphe magnus [152].…”

Section: Sensory Nervous Systemmentioning

confidence: 99%

Neurobiology in primary headaches

Edvinsson

Uddman

2005

Brain Research Reviews

212

209

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Section: Sensory Nervous Systemmentioning

confidence: 99%

Neurobiology in primary headaches

Edvinsson

Uddman

2005

Brain Research Reviews

212

209

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“…For example, in the CNS, N/OFQ has been shown to produce several effects such as pain modulation, stimulation of food intake and modulation of anxiety states [Calo et al, 2000]. In the periphery, activation of NOP receptors has been shown to produce significant effects on cardiovascular, genitourinary, gastrointestinal and respiratory systems [Fisher et al, 1998;Giuliani et al, 2000;Kapusta, 2000]. We have focused our attention on the pulmonary effects of N/OFQ where several reports have described an inhibitory effect of N/OFQ on non-adrenergic, non-cholinergic responses in the lungs [Fisher et al, 1998;Shah et al, 1998;Corboz et al, 2000Corboz et al, , 2001.…”

Section: Introductionmentioning

confidence: 99%

Antitussive Profile of the NOP Agonist Ro-64-6198 in the Guinea Pig

et al. 2004

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We have previously shown that N/OFQ, the endogenous peptide ligand for the ‘opioid-like’ NOP receptor, inhibits cough in guinea pigs and cats. In the present study we sought to continue our characterization of the cough-suppressant effects of NOP stimulation by profiling the pulmonary and antitussive effects of a novel non-peptide NOP agonist, Ro-64-6198, in guinea pigs. In receptor-binding assays, we confirmed that Ro-64-6198 selectively binds to NOP receptors over other opioid receptors. The K_i values for Ro-64-6198 at NOP, MOP, KOP and DOP receptors was 0.3, 36, 214 and 3,787 nmol/l, respectively. In GTPγS-binding assays, Ro-64-6198 displayed >900-fold functional selectivity at NOP relative to MOP receptors. We evaluated the effects of Ro-64-6198 (3 and 10 µmol/l) in isolated guinea pig nodose ganglia cells on the increases in intracellular Ca²⁺ concentration evoked by capsaicin stimulation (1 × 10^–8–1 × 10^–6 mol/l). Similar to previously reported data with N/OFQ, Ro-64-6198 (3 and 10 µmol/l) significantly attenuated Ca²⁺ responses in nodose ganglia cells produced by exposure to capsaicin. The effect of Ro-64-6198 (3 µmol/l) on capsaicin-induced intracellular Ca²⁺ responses was blocked by the NOP antagonist, J113397 (3 µmol/l). In guinea pig in vivo studies, aerosolized capsaicin (10–300 µmol/l) produced a dose-dependent increase in cough number. Ro-64-6198 given i.p. significantly inhibited cough due to capsaicin (300 µmol/l) exposure. In a duration study we found that the maximum antitussive effect (42 ± 8% inhibition) of Ro-64-6198 (3 mg/kg) was observed at 1 h after i.p. administration. Also at 1 h after administration, Ro-64-6198 (0.003–3.0 mg/kg, i.p.) produced a dose-dependent inhibition of cough. The antitussive effect of Ro-64-6198 (3 mg/kg, i.p.) was blocked by J113397 (12 mg/kg, i.p.) but not by the classical opioid antagonist naltrexone (10 mg/kg, i.p.). Although the antitussive action of Ro-64-6198 may be mediated by a central and/or a peripheral site of action, we hypothesize that selective oral NOP agonists that do not penetrate the blood-brain barrier may provide a novel approach for the treatment of cough. Moreover, because these drugs do not interact at MOP receptors, they may be devoid of codeine-like side effects such as respiratory depression, sedation, constipation or proclivities for addictive liabilities.

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“…This elution profiles resemble HPLC elution profile of rat dorsal spinal cord. 19) These unknown peaks might be fragments of nociceptin, containing the carboxy-terminal region (14)(15)(16)(17), since nociceptin has four critical enzymatic cleavage sites, and five main fragments (1-7), (1-11), (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), (12)(13)(14)(15)(16)(17), and (13)(14)(15)(16)(17). 26) Nociceptin is metabolized by aminoendopeptidase N and endopeptidase 24.15.…”

Section: Discussionmentioning

confidence: 99%

“…1,2) This neuropeptide is derived from the precursor prepronociceptin gene, which is expressed in the central nervous system and peripheral tissues. 3) Nociceptin has been shown to exert a variety of biological actions, some of which are opposite to those evoked by classical opioids. 4,5) Nociceptin has been implicated in the regulation of a variety of behaviors and physiological processes.…”

Section: Introductionmentioning

confidence: 99%

Application of an Enzyme Immunoassay for Nociceptin (Orphanin FQ)-like Immunoreactive Substances to Determination of the Human Plasma Levels

Naito

Takeyama

2003

JOURNAL OF HEALTH SCIENCE

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A sensitive and specific double-antibody enzyme immunoassay (EIA) for nociceptin (orphanin FQ)-like immunoreactive substances (nociceptin-IS) was developed. In competitive reactions, the nociceptin-antibody was incubated with both a nociceptin standard (or plasma extract sample) and β-D-galactosidase (β-Gal)-labeled synthetic human nociceptin (delayed addition method). The free and antibody-bound enzyme haptens were separated using an anti-rabbit IgG-coated immunoplate. The enzyme activity on the immunoplate was determined fluorometrically. The present immunoassay allows the detection of 15-700 pg/ml (sensitivity: 1.5 pg, 0.6 pg/well) of nociceptin. Using this EIA, the nociceptin-IS levels in human plasma were determined, and found to be in the range of 5.0 to 16.0 pg/ml. No circadian rhythms in the daytime (9:00-19:00) or effects of eating meals on human plasma nociceptin levels were found. We have established an evaluation system for both nociceptin-IS and substance P-IS levels in 1 ml of human plasma. As for the evaluation of analgesic effects of drugs and pain, this sensitive and specific EIA system for endogenous nociceptin may be valuable for clinical use.

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Nociceptin and neurotransmitter release in the periphery

Cited by 37 publications

References 54 publications

Neurobiology in primary headaches

Neurobiology in primary headaches

Antitussive Profile of the NOP Agonist Ro-64-6198 in the Guinea Pig

Application of an Enzyme Immunoassay for Nociceptin (Orphanin FQ)-like Immunoreactive Substances to Determination of the Human Plasma Levels

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