FMRF-amide and L-Arg-L-Phe increase blood pressure and heart rate in the anaesthetised rat by central stimulation of the sympathetic nervous system.
The neuropeptide FMRFamide (L-Phe-L-Met-L-Arg-L-Phe-NH2) increases mean arterial blood pressure (MABP) and heart rate (HR) in the anaesthetised rat at concentrations ranging from 10-1000 micrograms/kg. Here, we demonstrate that peptides containing L-arginyl-L-phenylalanine (L-Arg-L-Phe), the C-terminal sequence of FMRFamide, mimic its haemodynamic effects. L-Arg-L-Phe was approximately 4 fold more potent in increasing MABP and HR than FMRFamide. In 40 different peptides investigated, the following order of potency of the effective compounds was established: L-Arg-L-Phe-L-Ala = L-Arg-L-Phe greater than FMRFamide greater than L-Met-L-Arg-L-Phe = L-Arg-L-Trp greater than L-Arg-L-Tyr greater than D-Arg-L-Phe = L-Arg-L-Phe-OMe greater than L-Arg-L-Leu = L-Arg-L-Ile greater than L-Lys-L-Phe greater than L-Arg-L-Met. L-Arg-L-Phe or FMRFamide did not cause any pressor response in pithed rats, indicating a central mechanism of action. In anaesthetised rats, intravenous injections of FMRFamide or L-Arg-L-Phe (100 micrograms/kg) were associated with a 2-3 fold increase in plasma noradrenaline levels, whereas plasma adrenaline levels remained unchanged. Thus, L-Arg-L-Phe may represent the active principle of FMRFamide acting by a central mechanism involving the release of noradrenaline from sympathetic nerve terminals.
Thiemermann
C
C
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, United Kingdom.
al-Damluji
S
S
Hecker
M
M
Vane
J R
JR
D000595:Amino Acid Sequence; D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood; D019835:FMRFamide; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013564:Sympathetic Nervous System / Q000502:physiology*
D004151:Dipeptides; D009479:Neuropeptides; D009842:Oligopeptides; C067582:arginylphenylalanine; D019835:FMRFamide; D009638:Norepinephrine; D004837:Epinephrine