title: CART (85-102)-inhibition of psychostimulant-induced hyperlocomotion: importance of cyclization.
abstract: Synthetic derivative of C-terminal fragment of CART (55-102) with reduced thiol groups, [Abu(86,94)]CART (85-102)(red), given together with amphetamine (5 mg/kg, s.c.) or cocaine (15 mg/kg, s.c.), reversed hyperlocomotion induced by these drugs at a dose of 0.1 microg but not at a higher dose. In the cerebral cortex homogenate, [Abu(86,94)]CART (85-102)(red) was nonspecifically cleaved from N- and C-termini. This peptide contains two chemically blocked Cys residues, and two others in reduced form. Concomitant with cleavage, rapid cyclization occurred. The newly formed cyclic peptides were stable. The cyclic peptide [Abu(86,94)]CART (85-102)(ox) failed to inhibit amphetamine- and cocaine-induced locomotor activity. The ability to inhibit the locomotor-stimulant activity of amphetamine was retained in [Abu(86,88,94,101)]CART (85-102), in which all Cys were replaced with 2-aminobutyric acid to prevent their pairing. Disulfide bridge formation may be an interesting mechanism that prevents proteolysis of [Abu(86,94)]CART (85-102)(red) and terminates its ability to reverse amphetamine-induced hyperlocomotion.
authors.affiliation: Faculty of Chemistry and Regional Laboratory, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Dylag
authors.forename: Piotr
authors.initials: P
authors.lastname: Rafalski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kotlinska
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003553:Cystine / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D000662:Amphetamines; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011619:Psychotropic Drugs; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D003553:Cystine; D003042:Cocaine