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

摘要

class="enumerated" style="list-style-type:decimal">The cardiovascular effects by γ2-melanocyte-stimulating hormone (γ2-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 γ2-MSH(6–12), the most potent fragment of γ2-MSH.Mean arterial pressure (MAP) and heart rate (HR) changes were measured in conscious rats after intravenous administration of γ2-MSH related peptides.Phe-Arg-Trp-Asp-Arg-Phe-Gly (γ2-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. γ2-MSH(6–12) showed the most potent cardiovascular effects (ED50=12 nmol kg⁻¹ for ΔMAP; 7 nmol kg⁻¹ for ΔHR), as compared to the other Arg-Phe containing peptides (ED50=177–292 nmol kg⁻¹ for ΔMAP; 130–260 nmol kg⁻¹ for ΔHR).Peptides, which lack the C-terminal Arg-Phe sequence (Lys-Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Pro-Gly (γ2-pro¹¹-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.The results indicate that the baroreceptor reflex-mediated reduction of tonic sympathetic activity due to pressor effects is inhibited by γ2-MSH(6–12) and that its cardiovascular effects are dependent on the presence of a C-terminal Arg-Phe sequence.It is suggested that the FMRFa/NPFFa receptor is the likely candidate receptor, involved in these cardiovascular effects.