Nocistatin Inhibits 5-hydroxytryptamine Release in the Mouse Neocortex Via Presynaptic Gi/o Protein Linked Pathways

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2007 Jul 10

PMID 17618307

Citations 6

Authors

M Fantin

C Fischetti

C Trapella

M Morari

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Nocistatin (NST) is a neuropeptide generated from cleavage of the nociceptin/orphanin FQ (N/OFQ) precursor. Evidence has been presented that NST acts as a functional antagonist of N/OFQ, although NST receptor and transduction pathways have not yet been identified. We previously showed that N/OFQ inhibited [(3)H]5-hydroxytryptamine ([(3)H]5-HT) release from mouse cortical synaptosomes via activation of NOP receptors. We now investigate whether NST regulates [(3)H]5-HT release in the same preparation.

Experimental Approach: Mouse and rat cerebrocortical synaptosomes in superfusion, preloaded with [(3)H]5-HT and stimulated with 1 min pulses of 10 mM KCl, were used.

Key Results: Bovine NST (b-NST) inhibited the K(+)-induced [(3)H]5-HT release, displaying similar efficacy but lower potency than N/OFQ. b-NST action underwent concentration-dependent and time-dependent desensitization, and was not prevented either by the NOP receptor antagonist [Nphe(1) Arg(14),Lys(15)]N/OFQ(1-13)-NH(2) (UFP-101) or by the non-selective opioid receptor antagonist, naloxone. Contrary to N/OFQ, b-NST reduced [(3)H]5-HT release from synaptosomes obtained from NOP receptor knockout mice. However, both N/OFQ and NST were ineffective in synaptosomes pre-treated with the G(i/o) protein inhibitor, Pertussis toxin. NST-N/OFQ interactions were also investigated. Co-application of maximal concentrations of both peptides did not result in additive effects, whereas pre-application of maximal b-NST concentrations partially attenuated N/OFQ inhibition.

Conclusions And Implications: We conclude that b-NST inhibits [(3)H]5-HT release via activation of G(i/o) protein linked pathways, not involving classical opioid receptors and the NOP receptor. The present data strengthen the view that b-NST is, per se, a biologically active peptide endowed with agonist activity.

Citing Articles

Synthesis of Nocistatin C-terminal and its Amide Derivatives as an Opioid Peptide.

Sheikhhosseini E, Balalaie S, Bigdeli M Iran J Pharm Res. 2016; 15(3):337-342.

PMID: 27980568 PMC: 5149020.

Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems.

Toll L, Bruchas M, Calo G, Cox B, Zaveri N Pharmacol Rev. 2016; 68(2):419-57.

PMID: 26956246 PMC: 4813427. DOI: 10.1124/pr.114.009209.

Genetic and pharmacological evidence that endogenous nociceptin/orphanin FQ contributes to dopamine cell loss in Parkinson's disease.

Arcuri L, Viaro R, Bido S, Longo F, Calcagno M, Fernagut P Neurobiol Dis. 2016; 89:55-64.

PMID: 26804029 PMC: 5567676. DOI: 10.1016/j.nbd.2016.01.016.

Identification of NIPSNAP1 as a nocistatin-interacting protein involving pain transmission.

Okuda-Ashitaka E, Minami T, Tsubouchi S, Kiyonari H, Iwamatsu A, Noda T J Biol Chem. 2012; 287(13):10403-10413.

PMID: 22311985 PMC: 3322983. DOI: 10.1074/jbc.M111.271866.

Nocistatin and nociceptin modulate c-Fos expression in the mice thalamus.

Kazi J Neurol Sci. 2012; 33(6):1233-7.

PMID: 22240716 DOI: 10.1007/s10072-012-0933-0.

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