PAVE: Physiological functions of PACAP / VIP receptors in the nervous system

• Forschungsstelle: EU FRP
• Projektnummer: 98.0257
• Projekttitel Englisch: PAVE: Physiological functions of PACAP / VIP receptors in the nervous system

Schlüsselwörter (Englisch)

Energy metabolism; neuron; astrocyte; glucose; glycogen; VIP; PACAP

Alternative Projektnummern (Englisch)

EU project number: BIO4-CT98-0517

Forschungsprogramme (Englisch)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Kurzbeschreibung (Englisch)

See abstract

Partner und Internationale Organisationen (Englisch)

Coordinator:CNRS MMCC Montpellier (F)

Abstract (Englisch)

This component of the project was aimed to develop in vitro functional assays to test VIP/PACAP analogues. The first assay involves the regulation of glycogen metabolism in cortical astrocytes. Thus, by applying VIP/PACAP to cortical astrocytes, it is possible to detect a short-term (minutes) response i.e. glycogenolysis, and a long-term (hours) transcriptionally-regulated response, i.e. glycogen synthesis. In the course of this study, we have extended these findings by showing that stimulation of cortical astrocytes by VIP/PACAP also increases the expression of Protein Targeting to Glycogen, a protein that serves as a ' scaffold ' for efficient activation of glycogen synthesis. The physiological response to VIP- or PACAP-mediated PTG induction is the funnelling of all available substrates into glycogen resynthesis. In addition to regulating glycogen levels and PTG expression in astrocytes, VIP and PACAP also stimulate glucose utilization in cultured cortical neurons. The increase in glucose utilization by VIP/PACAP is a long-term effect that is dependent on transcription. Consistent with this observation, VIP/PACAP-induced glucose utilization is accompanied by an increase in the expression of the neuronal glucose transporter GLUT3. The effects of VIP and PACAP are mediated through the PAC1-prefering type 1 receptor that is PAC1. Since neurons exhibit VIP/PACAP receptor subtypes that are different from astrocytes, stimulation of GLUT3 expression and glucose utilization by VIP/PACAP in cortical neurons represents another assay suitable to test VIP/PACAP analogues. Thus, this component has contributed to the development of in vitro assays to test the efficacy of VIP/PACAP analogues as initially planed.

Datenbankreferenzen (Englisch)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 98.0257