Dépôt numérique

How specific are the antagonists of PACAP receptors

Doan, Ngoc Duc; Bourgault, Steve; Létourneau, Myriam; Vaudry, David; Detheux, Michel; Vaudry, Hubert; Chatenet, David ORCID logoORCID: 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.

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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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