Relevance of the C-terminal Arg-Phe sequence in γ2-melanocyte-stimulating hormone (γ2-MSH) for inducing cardiovascular effects in conscious rats

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-Cln-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 (ED50 = 12 nmol kg(-1) for Delta MAP: 7 nmol kg(-1) for Delta HR), as compared to the other Arg-Phe containing peptides (ED50 = 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 presser 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.