Neuropeptide Y and gamma-melanocyte stimulating hormone (gamma-MSH) share a common pressor mechanism of action.
Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes both of these C-terminal motifs. We now present evidence that an antagonist with Y1 and RFamide receptor activity, BIBO3304, will attenuate the central cardiovascular effects of both gamma-melanocyte stimulating hormone (gamma-MSH) and NPY. The use of synthetic melanocortin and NPY peptide analogs excluded an interaction with melanocortin or Y family receptors. We suggest that the anatomical convergence of NPY and melanocortin neurons on cardiovascular control centers may have pathophysiological implications through a common or similar RFamide receptor(s), much as they converge on other nuclei to coordinately control energy homeostasis.
The Center for the Study of Weight Regulation and Associated Disorders and The Vollum Institute, Oregon Health and Science University, Portland, OR 97239-3098, USA.
Kenneth A
KA
Gruber
Wei
W
Fan
Helena
H
Akerberg
Dan
D
Larhammar
Melissa J S
MJ
Chee
William F
WF
Colmers
Roger D
RD
Cone
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D016466:CHO Cells; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019825:gamma-MSH / Q000378:metabolism / Q000502:physiology*
D006727:Hormone Antagonists; D009478:Neuropeptide Y; D019825:gamma-MSH; D001120:Arginine; C117416:BIBO 3304