Partial agonist activity of R3(BΔ23-27)R/I5 at RXFP3--investigation of in vivo and in vitro pharmacology.
Eur J Pharmacol
; 747: 123-31, 2015 Jan 15.
Article
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| MEDLINE
| ID: mdl-25496752
ABSTRACT
Relaxin family peptide receptor 3 (RXFP3) is a G-protein coupled receptor mainly expressed in the brain and involved in appetite regulation. Previous studies in lean Wistar rats during the light phase have shown that the chimeric peptide R3(BΔ23-27)R/I5 suppresses food intake stimulated by an RXFP3 agonist, but has no effect on food intake when administered alone. We wanted to further investigate if R3(BΔ23-27)R/I5 on its own is able to antagonize the basal tone of the relaxin-3/RXFP3 system and therefore characterized the pharmacology of R3(BΔ23-27)R/I5 in vivo and in vitro. R3(BΔ23-27)R/I5 was intracerebroventricularly (ICV) injected in diet induced obese (DIO) Wistar rats and food intake was automatically measured during the dark phase when feeding drive is high. In our hands, R3(BΔ23-27)R/I5 alone did not have a significant effect on food intake during 24h following administration. Consistent with previous results, relaxin-3 stimulated food intake in satiated lean rats. R3(BΔ23-27)R/I5 was characterized in vitro using [(35)S]-GTPγS binding and cAMP assays, both assessing Gαi-protein mediated signalling, and dynamic mass redistribution (DMR) assays capturing the integrated cell response. R3(BΔ23-27)R/I5 showed partial agonist activity in all three functional assays. Thus, since R3(BΔ23-27)R/I5 displays partial RXFP3 agonist properties in vitro, further in vivo studies including additional tool compounds are needed to address if antagonizing relaxin-3/RXFP3 basal tone is a therapeutically relevant mechanism to regulate food intake and body weight.
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Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Proteínas Recombinantes
/
Receptores de Péptidos
/
Fármacos Antiobesidad
/
Receptores Acoplados a Proteínas G
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suecia