Article date: December 2000
By: M J M A Nijsen, G J W De Ruiter, C M Kasbergen, P Hoogerhout, D J De Wildt in Volume 131, Issue 7, pages 1468-1474
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.
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.
British Journal of Pharmacology (2000) 131, 1468–1474; doi:10.1038/sj.bjp.0703709
DOI: 10.1038/sj.bjp.0703709
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