Structure-activity relationship and signal transduction of gamma-MSH peptides in GH3 cells: further evidence for a new melanocortin receptor.
The structure-activity relationship and signal transduction properties of the pro-opiomelanocortin (POMC)-derived gamma-MSH peptides in the GH3 cell line was compared with that described for the known melanocortin receptors (MCRs). Single alanine replacements showed that, unlike the classical MCRs, the His(5)-Phe(6)-Arg(7)-Trp(8) sequence in gamma2-MSH is not a core sequence for activating the gamma-MSH receptor in GH3 cells, whereas Met(3) is essential. gamma2-MSH increased binding of [35S]GTPgammaS to membrane preparations of GH3 cells. Blockade of protein kinase A abolished the [Ca(2+)](i) responses to gamma3-MSH, and low nanomolar doses of gamma3-MSH increased intracellular cAMP levels, which could be blocked by pertussis toxin (PTX). We conclude that the putative novel gamma-MSH receptor in GH3 cells is a GPCR, but with structure-activity and signal transduction features different from those of the classical MCRs.
Laboratory of Cell Pharmacology, K.U. Leuven, Medical School, Campus Gasthuisberg (O & N), B-3000, Leuven, Belgium.
Lies
L
Langouche
Katrien
K
Pals
Carl
C
Denef
D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D037342:Pertussis Toxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018043:Receptors, Corticotropin / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D044101:Receptors, Melanocortin; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection; D019825:gamma-MSH / Q000737:chemistry* / Q000502:physiology
D010455:Peptides; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D019825:gamma-MSH; C086971:melanocortin 5 receptor; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; D037342:Pertussis Toxin; D000409:Alanine; D002118:Calcium