VPAC2-R mediates the lipolytic effects of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide in primary rat adipocytes.
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.
Akesson
Lina
L
Section for Molecular Signaling, Department of Cell and Molecular Biology, Biomedical Center C11, Lund University, SE-221 84 Lund, Sweden. lina@akesson@.nu
Ahrén
Bo
B
Edgren
Gudrun
G
Degerman
Eva
E
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology*
C495403:Adcyap1 protein, rat; C495505:Adcyap1r1 protein, rat; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C495508:Vipr1 protein, rat; C495511:Vipr2 protein, rat; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D014660:Vasoactive Intestinal Peptide; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases