Insulin-relaxin family peptide signaling and receptors in mouse brain membranes and neuronal cells.
Several orphan G-protein-coupled receptors (GPCRs), LGR7 and LGR8, GPCR135 and GPCR142, were recently identified as putative, native receptors for different relaxin-family peptides, and their cell signaling mechanisms were elucidated in stably transfected cell lines. Anatomic studies have demonstrated that discrete populations of neurons in rat brain express relaxin and relaxin-3 mRNA/peptide, relaxin and relaxin-3 binding sites, and LGR7 and GPCR135 mRNAs. Thus, we began to assess the ability of relaxin-family peptides to alter cAMP production in brain and the involvement of the different native receptors. In mouse cortical membranes, a fixed concentration of relaxin peptides (100 nM) inhibited forskolin-induced cAMP production, but further studies in normal and receptor knockout mouse strains are required to assess the specificity of these effects. In addition, whole-cell signaling mechanisms are being investigated in a mouse hypothalamic cell line, GT1-7. Such studies will help to establish the actions of relaxin-family peptides via their different GPCRs in different brain pathways.
Ortinau
Stefanie
S
Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria 3010, Australia.
Lin
Feng
F
Wade
John D
JD
Tregear
Geoffrey W
GW
Bathgate
Ross A D
RA
Gundlach
Andrew L
AL
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000145:classification / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000378:metabolism*; D012065:Relaxin / Q000145:classification / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin; D000242:Cyclic AMP; D011972:Receptor, Insulin