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Melanocortins and cardiovascular regulation
D H Versteeg1, P Van Bergen, R A Adan
1Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, Utrecht University, Netherlands. d.h.g.versteeg@med.uu.nl
European Journal of Pharmacology
|December 9, 1998
Summary
Melanocortins, peptides sharing a common core sequence, influence cardiovascular function through various mechanisms. Research suggests specific gamma-melanocyte-stimulating hormones (gamma-MSHs) increase blood pressure by acting on central nervous system receptors.
Area of Science:
- Endocrinology
- Cardiovascular Physiology
- Neuroscience
Background:
- Melanocortins are pro-opiomelanocortin-derived peptides with a conserved His-Phe-Arg-Trp core sequence.
- These peptides are known to exert diverse cardiovascular effects.
- Understanding their mechanisms of action is crucial for cardiovascular research.
Purpose of the Study:
- To review the sites and mechanisms of melanocortin action on cardiovascular function.
- To focus on the cardiovascular effects of gamma-melanocyte-stimulating hormones (gamma-MSHs).
- To contextualize findings within current knowledge of melanocortin receptor subtypes and agonist selectivity.
Main Methods:
- Review of existing literature on melanocortin actions.
- Analysis of structure-activity relationships for various melanocortins.
- Examination of in vivo and in vitro data regarding receptor binding and physiological responses.
Main Results:
- gamma2-MSH and related peptides induce pressor and tachycardiac effects, likely via central receptors in the anteroventral third ventricle (AV3V) region, increasing sympathetic outflow.
- ACTH-(1-24) causes a depressor effect, potentially mediated by peripheral MC2 receptors.
- Melanocortins improve cardiovascular function in experimental hemorrhagic shock, though receptor mediation remains unclear for some peptides.
Conclusions:
- The cardiovascular effects of melanocortins are complex and receptor-dependent.
- Central mechanisms involving sympathetic outflow are implicated in the pressor effects of gamma-MSHs.
- Further research, particularly with selective antagonists, is needed to fully elucidate melanocortin receptor roles in cardiovascular regulation.