Doan, Ngoc Duc; Bourgault, Steve; Létourneau, Myriam; Vaudry, David; Detheux, Michel; Vaudry, Hubert; Chatenet, David 
ORCID: https://orcid.org/0000-0002-7270-4328 et Fournier, Alain
(2012).
How specific are the antagonists of PACAP receptors
In: 10th International Symposium on VIP-PACAP and Related Peptides, December 13-16, 2011, Eilat, ISRAEL.
Résumé
The Pituitary Adenylate-Cyclase Activating Polypeptide
(PACAP), a hypophysiotropic neurohormone, exerts pleiotropic actions via the activation of three different G-protein
coupled receptors, named PAC1, VPAC1 and VPAC2. In
order to discriminate downstream signalling pathways and
effects associated with their respective activation, selective
antagonists were developed. PACAP(6-38) and (d.24-42)
Maxadilan are currently considered as PAC1-selective antagonists and have been used in several studies in order to
investigate PAC1-associated biological activities. However,
recent study has demonstrated that Maxadilan and
PACAP differed in their mode of activation, suggesting
that maxadilan-based antagonists might not be suitable
for investigating PACAP receptor-associated action following activation. The goal of the present study was to
characterize the pharmacological profile of three
PACAP-based antagonists, i.e. PACAP(6-38), [D-Pro2
]
PACAP38 and [Sar4
]PACAP38. To do so, these analogs
were pharmacologically characterized using a radioligand
binding assay and an intracellular calcium mobilization
assay, using three cell lines stably transfected with the
PAC1, VPAC1 and VPAC2 receptors, respectively. The
results showed that these compounds are all able to bind to
these receptors. Although PACAP(6-38) is unable to
increase intracellular calcium mobilization, [D-Pro2
]
PACAP38 and [Sar4
]PACAP38 slightly activate PAC1
and VPAC1 receptors at 10-5 M. Preliminary results
regarding their antagonist activity show that these peptides
are able to inhibit the intracellular calcium released by
PACAP38 (10-9 M). Although further studies are needed,
these results open up a new view and consideration in
using existing PACAP-based antagonists to control and/or
study signalling pathways or effects of PACAP or its
derivatives.
| Type de document: | Document issu d'une conférence ou d'un atelier |
|---|---|
| Informations complémentaires: | Affiche Scientifique Journal of Molecular Neuroscience 48(suppl.1):S161 |
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 28 janv. 2024 14:55 |
| Dernière modification: | 28 janv. 2024 14:55 |
| URI: | https://espace.inrs.ca/id/eprint/14120 |
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