Relevance of the C‐terminal Arg‐Phe sequence in γ2‐melanocyte‐stimulating hormone (γ2‐MSH) for inducing cardiovascular effects in conscious rats
Open accessAbstract
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.
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The Arg-Phe sequence in γ-MSH is critical for its acute hypertensive actions since synthetic analog peptides lacking this sequence do not raise blood pressure.
“The Arg-Phe sequence in γ-MSH is critical for its acute hypertensive actions since synthetic analog peptides lacking this sequence do not raise BP [16, 17].”
From Role of the brain melanocortins in blood pressure regulation (2017) · cites this paper as [16]
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- Authors
- Nijsen, M. J. M. A., De Ruiter, G. J. W., Kasbergen, C. M., Hoogerhout, P., & De Wildt, D. J.
- Affiliations
- Utrecht University (NL)
- National Institute for Public Health and the Environment (NL)
- Corresponding author
- Nijsen, M J M A
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 131
- Issue
- 7
- Pages
- 1468-1474
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1572467
- OpenAlex
- W2048680731
- Cited by
- 24
- References
- 43
- Citations by year
- 2020: 1 · 2017: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- cardiovascular effects, hemodynamic response, neuropeptide FF, met-enkephalin, mean arterial pressure, heart rate, conscious rats, peptide analogues
- MeSH terms
- Amino Acid Sequence, Amino Acids, Animals, Blood Pressure, Cardiovascular Physiological Phenomena, Consciousness, Dose-Response Relationship, Drug, Heart Rate, Male, Oligopeptides, Rats, Wistar, gamma-MSH, Amino Acid Substitution, Rats
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