title: Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists.
abstract: Neuropeptide S (NPS) regulates various biological functions by activating the NPS receptor (NPSR). Previous studies demonstrated that the substitution of Gly(5) with d-amino acids generates NPSR antagonists. Eleven [d-Xaa(5)]NPS derivatives were synthesized and pharmacologically tested measuring [Ca(2+)](i) in HEK293(mNPSR) cells. The results confirmed that the [d-Xaa(5)] substitution promotes antagonist activity with potency inversely related to the side chain size and allowed identification of the novel potent NPSR peptide antagonist [(t)Bu-d-Gly(5)]NPS.
authors.affiliation: Department of Pharmaceutical Sciences and Biotechnology Center and Department of Experimental and Clinical Medicine, Section of Pharmacology and Neuroscience Center, National Institute of Neuroscience, Univ. of Ferrara, Ferrara, Italy. r.guerrini@unife.it
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Valeria
authors.initials: V
authors.lastname: Camarda
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Girolamo
authors.initials: G
authors.lastname: Caló
authors.forename: Anna
authors.initials: A
authors.lastname: Rizzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruzza
authors.forename: Stella
authors.initials: S
authors.lastname: Fiorini
authors.forename: Erika
authors.initials: E
authors.lastname: Marzola
authors.forename: Rainer K
authors.initials: RK
authors.lastname: Reinscheid
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
mesh_terms: D002118:Calcium / Q000032:analysis; D002460:Cell Line; D055808:Drug Discovery; D006801:Humans; D009479:Neuropeptides / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: C484532:NPSR1 protein, human; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; C506531:neuropeptide S, human; D002118:Calcium