title: Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors.
abstract: It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg(7)]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals. We have pursued further modification on the [des-Arg(7)]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. Electronic address: yeon@email.arizona.edu.
authors.forename: Yeon Sun
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hall
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Cyf
authors.initials: C
authors.lastname: Ramos-Colon
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Remesic
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: LeBaron
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: David
authors.initials: D
authors.lastname: Rankin
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.affiliation: Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. Electronic address: hruby@email.arizona.edu.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004399:Dynorphins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D018002:Receptors, Bradykinin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018002:Receptors, Bradykinin; D004399:Dynorphins
keywords: Amphipathicity; Anti-hyperalgesic effect; Bradykinin receptors; Dynorphin A; Non-opioid