PMID- 9578554
OWN - NLM
STAT- MEDLINE
DCOM- 19980604
LR  - 20220311
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 37
IP  - 19
DP  - 1998 May 12
TI  - Differential intracellular signaling of the GalR1 and GalR2 galanin receptor 
      subtypes.
PG  - 6711-7
AB  - The diverse physiological functions exerted by the neuropeptide galanin may be 
      regulated by multiple G protein-coupled receptor subtypes and intracellular 
      signaling pathways. Three galanin receptor subtypes (GalRs) have been recently 
      cloned, but the G protein coupling profiles of these receptors are not completely 
      understood. We have generated GalR1- and GalR2-expressing Chinese hamster ovary 
      (CHO) cell lines and systematically examined the potential for these two 
      receptors to couple to the Gs, Gi, Go, and Gq proteins. Galanin did not stimulate 
      an increase in cAMP levels in GalR1/CHO or GalR2/CHO cells, suggesting an 
      inability of either receptor to couple to Gs. Galanin inhibited 
      forskolin-stimulated cAMP production in GalR1/CHO cells by 70% and in GalR2/CHO 
      cells by 30%, suggesting a strong coupling of GalR1 to Gi and a more modest 
      coupling between GalR2 and Gi. GalR1 and GalR2 both mediated pertussis 
      toxin-sensitive MAPK activity (2-3-fold). The stimulation mediated by GalR1 was 
      inhibited by expression of the C-terminus of beta-adrenergic receptor kinase 
      (beta ARKct), which specifically inhibits G beta gamma signaling, but was not 
      affected by the protein kinase C (PKC) inhibitor, bis[indolylmaleimide], or 
      cellular depletion of PKC. In contrast, GalR2-mediated MAPK activation was not 
      affected by beta ARKct expression but was abolished by inhibition of PKC 
      activity. The data demonstrate that GalR1 is coupled to a Gibetagamma signaling 
      pathway to mediate MAPK activation. In contrast, GalR2 utilizes a distinct 
      signaling pathway to mediate MAPK activation, which is consistent with 
      Go-mediated MAPK activation in CHO cells. Galanin was unable to stimulate 
      inositol phosphate (IP) accumulation in CHO or COS-7 cells expressing GalR1. In 
      contrast, galanin stimulated a 7-fold increase in IP production in CHO or COS-7 
      cells expressing GalR2. The GalR2-mediated IP production was not affected by 
      pertussis toxin, suggesting a linkage of GalR2 with Gq/G11. Thus, the GalR1 
      receptor appears to activate only the Gi pathway. By contrast, GalR2 is capable 
      of stimulating signaling which is consistent with activation of Go, Gq/G11, and 
      Gi. The differential signaling profiles and the tissue distribution patterns of 
      GalR1 and GalR2 may underlie the functional spectra of galanin action mediated by 
      these galanin receptors and regulate the diverse physiological functions of 
      galanin.
FAU - Wang, S
AU  - Wang S
AD  - Department of CNS/CV Biological Research, Schering-Plough Research Institute, 
      Kenilworth, New Jersey 07033, USA. suke.wang@spcorp.com
FAU - Hashemi, T
AU  - Hashemi T
FAU - Fried, S
AU  - Fried S
FAU - Clemmons, A L
AU  - Clemmons AL
FAU - Hawes, B E
AU  - Hawes BE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Receptors, Galanin)
RN  - 0 (Receptors, Gastrointestinal Hormone)
RN  - 88813-36-9 (Galanin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Cyclic AMP/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Galanin/metabolism/pharmacology
MH  - Intracellular Fluid/*metabolism/physiology
MH  - Rats
MH  - Receptors, Galanin
MH  - Receptors, Gastrointestinal Hormone/biosynthesis/genetics/*physiology
MH  - *Signal Transduction/drug effects/genetics
MH  - Swine
MH  - Transfection
EDAT- 1998/06/06 00:00
MHDA- 1998/06/06 00:01
CRDT- 1998/06/06 00:00
PHST- 1998/06/06 00:00 [pubmed]
PHST- 1998/06/06 00:01 [medline]
PHST- 1998/06/06 00:00 [entrez]
AID - bi9728405 [pii]
AID - 10.1021/bi9728405 [doi]
PST - ppublish
SO  - Biochemistry. 1998 May 12;37(19):6711-7. doi: 10.1021/bi9728405.