1. The cardiovascular effects by gamma(2)-melanocyte-stimulating
hormone (gamma(2)-MSH) are probably not due to any of the well-known
melanocortin subtype receptors. We hypothesize that the receptor for
Phe-Met-Arg-Phe-amide (FMRFa) or
Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-
amide (
neuropeptide FF; NPFFa), other Arg-Phe containing
peptides, is the candidate receptor. Therefore, we studied various Arg-Phe containing
peptides to compare their haemodynamic profile with that of gamma(2)-MSH(6 - 12), the most potent fragment of gamma(2)-MSH. 2. Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after
intravenous administration of gamma(2)-MSH related
peptides. 3.
Phe-Arg-Trp-Asp-Arg-
Phe-Gly (gamma(2)-MSH(6 - 12)), FMRFa, NPFFa,
Met-enkephalin-Arg-Phe-
amide (MERFa), Arg-Phe-
amide (RFa), acetyl-Phe-norLeu-Arg-Phe-
amide (acFnLRFa) and desamino-Tyr-Phe-norLeu-Arg-Phe-
amide (daYFnLRFa) caused a dose-dependent increase in MAP and HR. gamma(2)-MSH(6 - 12) showed the most potent cardiovascular effects (ED(50)=12 nmol kg(-1) for delta MAP; 7 nmol kg(-1) for delta HR), as compared to the other Arg-Phe containing
peptides (ED(50)=177 - 292 nmol kg(-1) for delta MAP; 130 - 260 nmol kg(-1) for delta HR). 4.
Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-
Met-Gly-
His-Phe-Arg-Trp-Asp-
Arg-Pro-Gly (gamma(2)-pro(11)-
MSH), desamino-Tyr-Phe-norLeu-Arg-[L-1,2,3,4
tetrahydroisoquinoline-3-
carboxylic acid]-
amide (daYFnLR[
TIC]a) and
Met-enkephalin (ME)), were devoid of cardiovascular actions. 5. The results indicate that the baroreceptor reflex-mediated reduction of tonic sympathetic activity due to pressor effects is inhibited by gamma(2)-MSH(6 - 12) and that its cardiovascular effects are dependent on the presence of a C-terminal Arg-Phe sequence. 6. It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular effects.