Advanced

VPAC2-R Mediates the Lipolytic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide in Primary Rat Adipocytes.

Åkesson, Lina LU ; Ahrén, Bo; Edgren, Gudrun and Degerman, Eva (2005) In Endocrinology 146(2). p.744-750
Abstract
The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally and functionally related. Their actions have been shown to be mediated by three different receptor subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2-R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38 induces lipolysis in rat adipocytes, and in the present study we examined whether VIP has similar effects and which of the three receptors mediates this PACAP/VIP action. We showed by RT-PCR that all three receptor subtypes are present in rat adipocytes. We demonstrated that VIP (1-100 nM), like PACAP38, stimulates lipolysis in isolated adipocytes,... (More)
The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally and functionally related. Their actions have been shown to be mediated by three different receptor subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2-R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38 induces lipolysis in rat adipocytes, and in the present study we examined whether VIP has similar effects and which of the three receptors mediates this PACAP/VIP action. We showed by RT-PCR that all three receptor subtypes are present in rat adipocytes. We demonstrated that VIP (1-100 nM), like PACAP38, stimulates lipolysis in isolated adipocytes, as determined by glycerol release. By a pharmacological approach, using antagonists and agonists specific for the receptor subtypes, we elucidated the mechanisms by which PACAP38 and VIP mediate their lipolytic effects. We found that antagonists of PAC1-R [PACAP(6-38)] and VPAC1-R (PG97-269) did not affect lipolysis induced by 0.1-100 nM PACAP38 or VIP, and that a VPAC1-R agonist [K15, R16, L27VIP(1-7) GRF(8-27)] did not affect lipolysis at 1-1000 nM. However, two different VPAC2-R agonists [Hexa-VIP(1-28) and Ro25-1553] clearly mimicked the lipolytic effect of PACAP38 and VIP. In addition, the VPAC2-R antagonist PG99-465 (100 nM) caused right-shifted dose-response curves of PACAP38- and VIP-induced lipolysis. These results therefore provide evidence that all three PACAP/VIP receptor subtypes are expressed in primary rat adipocytes, but that the VPAC2-R subtype is responsible for mediating the lipolytic effects induced by PACAP38 and VIP. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Endocrinology
volume
146
issue
2
pages
744 - 750
publisher
Endocrine Society
external identifiers
  • pmid:15514088
  • wos:000226295300025
  • scopus:12344299315
ISSN
0013-7227
DOI
10.1210/en.2004-0504
language
English
LU publication?
yes
id
03c67119-6a12-45b3-ba08-75468838217c (old id 131059)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15514088&dopt=Abstract
date added to LUP
2007-06-27 09:02:01
date last changed
2017-01-08 03:51:21
@article{03c67119-6a12-45b3-ba08-75468838217c,
  abstract     = {The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are structurally and functionally related. Their actions have been shown to be mediated by three different receptor subtypes: PAC1-R, which has exclusive affinity for PACAP, and VPAC1-R and VPAC2-R, which have equal affinity for PACAP and VIP. We recently showed that PACAP38 induces lipolysis in rat adipocytes, and in the present study we examined whether VIP has similar effects and which of the three receptors mediates this PACAP/VIP action. We showed by RT-PCR that all three receptor subtypes are present in rat adipocytes. We demonstrated that VIP (1-100 nM), like PACAP38, stimulates lipolysis in isolated adipocytes, as determined by glycerol release. By a pharmacological approach, using antagonists and agonists specific for the receptor subtypes, we elucidated the mechanisms by which PACAP38 and VIP mediate their lipolytic effects. We found that antagonists of PAC1-R [PACAP(6-38)] and VPAC1-R (PG97-269) did not affect lipolysis induced by 0.1-100 nM PACAP38 or VIP, and that a VPAC1-R agonist [K15, R16, L27VIP(1-7) GRF(8-27)] did not affect lipolysis at 1-1000 nM. However, two different VPAC2-R agonists [Hexa-VIP(1-28) and Ro25-1553] clearly mimicked the lipolytic effect of PACAP38 and VIP. In addition, the VPAC2-R antagonist PG99-465 (100 nM) caused right-shifted dose-response curves of PACAP38- and VIP-induced lipolysis. These results therefore provide evidence that all three PACAP/VIP receptor subtypes are expressed in primary rat adipocytes, but that the VPAC2-R subtype is responsible for mediating the lipolytic effects induced by PACAP38 and VIP.},
  author       = {Åkesson, Lina and Ahrén, Bo and Edgren, Gudrun and Degerman, Eva},
  issn         = {0013-7227},
  language     = {eng},
  number       = {2},
  pages        = {744--750},
  publisher    = {Endocrine Society},
  series       = {Endocrinology},
  title        = {VPAC2-R Mediates the Lipolytic Effects of Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide in Primary Rat Adipocytes.},
  url          = {http://dx.doi.org/10.1210/en.2004-0504},
  volume       = {146},
  year         = {2005},
}