Nociceptin inhibits cough in the guinea‐pig by activation of ORL₁ receptors

Abstract

We studied the central and peripheral antitussive eect of ORL 1 receptor activation with nociceptin/ orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 mg) given directly into the CNS by an intracerebroventricular (i. ) also inhibited cough approximately by 25 and 42%, respectively. These ®ndings indicate that selective ORL 1 agonists display the potential to inhibit cough by both a central and peripheral mechanism, and potentially represent a novel therapeutic approach for the treatment of cough.

[Arg14,Lys15]Nociceptin, a Highly Potent Agonist of the Nociceptin/Orphanin FQ Receptor: in Vitro and in Vivo Studies

“…J-113397 is a nonpeptide compound recently identified by investigators at Banyu as a selective antagonist of the recombinant human OP 4 receptor (Kawamoto et al, 1999). The antagonist properties and selectivity of action of J-113397 have later been confirmed in vitro on the native OP 4 receptor expressed in isolated tissues (Bigoni et al, 2000;Corboz et al, 2000) and in several in vivo studies (Ozaki et al, 2000;Ueda et al, 2000;McLeod et al, 2001 Bigoni et al, 2000;Calo' et al, 2000b) These data indicate that the addition of two positively charged residues, Arg 14 and Lys 15 , to the sequence of NC leads to increased potency, possibly through an increase in receptor affinity. However, Okada et al (2000) than the natural peptide.…”

“…Its effects are long-lasting in vivo. This analog can be considered a novel pharmacological tool for the investigation of the neurobiology of the NC/OP 4 receptor system, in particular for clarifying the therapeutic potential of OP 4 receptor agonists as anxiolytics (Jenck et al, 1997), antianorectics (Ciccocioppo et al, 2001), and antitussives (McLeod et al, 2001), or as novel agents to be used for the treatment of drug abuse (Ciccocioppo et al, 2000), cardiovascular (Salis et al, 2000) or renal (Kapusta, 2000) diseases, and urinary incontinence (Lecci et al, 2000;Lazzeri et al, 2001). …”

Blockade of Nociceptin/Orphanin FQ Receptor Signaling in Rat Substantia Nigra Pars Reticulata Stimulates Nigrostriatal Dopaminergic Transmission and Motor Behavior

“…Different from that reported for the mesoaccumbal pathway in the mouse (Koizumi et al, 2004), however, an N/OFQergic inhibitory tone on the nigrostriatal transmission was disclosed because NOP receptor antagonists given into the SNr facilitated striatal DA release. This facilitation was likely a result of NOP receptor blockade because it was consistently observed with chemically unrelated molecules, delivered to the SNr via different routes, at doses reported to selectively affect N/OFQ responses (for UFP-101, see Calò et al, 2002;Koizumi et al, 2004;Kuzmin et al, 2004;for J-113397 see, Ozaki et al, 2000;Ueda et al, 2000;McLeod et al, 2001;Lutfy et al, 2002). Tonic N/OFQergic control of the nigrostriatal DAergic transmission was disclosed only in vivo because UFP-101 did not affect firing activity in nigral slices.…”

The diagnosis and management of chronic cough

“…Nociceptin, which binds to opioid receptor-like (ORL)-1 receptors, inhibits sensory nerve function in guinea pig airways, and i.v. or centrally administered nociceptin inhibits cough by activating inhibitory ORL1 receptor on sensory nerve terminals [110,111]. Gamma aminobutyric acid (GABA) B receptor agonists have a similar inhibitory profile on the tussive response [112].…”