Melanocortin antagonists define two distinct pathways of cardiovascular control by α- and γ-melanocyte-stimulating hormones

Si Jia Li, Károly Varga, Phillip Archer, Victor J Hruby, Shubh D. Sharma, Robert A. Kesterson, Roger D. Cone, George Kunos

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Melanocortin peptides and at least two subtypes of melanocortin receptors (MC3-R and MC4-R) are present in brain regions involved in cardiovascular regulation. In urethane-anesthetized rats, unilateral microinjection of α-melanocyte-stimulating hormone (MSH) into the medullary dorsal-vagal complex (DVC) causes dose-dependent (125-250 pmol) hypotension and bradycardia, whereas γ-MSH is less effective. The effects of α-MSH are inhibited by microinjection to the same site of the novel MC4-R/MC3-R antagonist SHU9119 (2-100 pmol) but not naloxone (270 pmol), whereas the similar effects of intra-DVC injection of β-endorphin (1 pmol) are inhibited by naloxone and not by SHU9119. Hypotensive and bradycardic responses to electrical stimulation of the arcuate nucleus also are inhibited by ipsilateral intra-DVC microinjection of SHU9119. γ-MSH and ACTH(4-10), but not α-MSH, elicit dose-dependent (0.1-12.5 nmol) pressor and tachycardic effects, which are much more pronounced after intracarotid than after intravenous administration. The effects of γ-MSH (1.25 nmol) are not inhibited by the intracarotid injection of SHU9119 (1.25-12.5 nmol) or the novel MC3-R antagonist SHU9005 (1.25-12.5 nmol). We conclude that the hypotension and bradycardia elicited by the release of α-MSH from arcuate neurons is mediated by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the similar effects of β-endorphin, a peptide derived from the same precursor, are mediated by opiate receptors at the same site. In contrast, neither MC3-R nor MC4-R is involved in the centrally mediated pressor and tachycardic actions of γ-MSH, which, likely, are mediated by an as yet unidentified receptor.

Original languageEnglish (US)
Pages (from-to)5182-5188
Number of pages7
JournalJournal of Neuroscience
Volume16
Issue number16
StatePublished - Aug 15 1996

Fingerprint

Melanocortins
Melanocyte-Stimulating Hormones
Microinjections
Melanocortin Receptors
Endorphins
ACTH (4-10)
Bradycardia
Naloxone
Hypotension
Arcuate Nucleus of Hypothalamus
Peptides
Injections
Urethane
Opioid Receptors
Sensory Receptor Cells
Intravenous Administration
Electric Stimulation
Neurons
SHU 9119

Keywords

  • α-MSH
  • γ-MSH
  • blood pressure
  • dorsal-vagal complex
  • heart rate
  • melanocortin antagonists
  • melanocortin receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Li, S. J., Varga, K., Archer, P., Hruby, V. J., Sharma, S. D., Kesterson, R. A., ... Kunos, G. (1996). Melanocortin antagonists define two distinct pathways of cardiovascular control by α- and γ-melanocyte-stimulating hormones. Journal of Neuroscience, 16(16), 5182-5188.

Melanocortin antagonists define two distinct pathways of cardiovascular control by α- and γ-melanocyte-stimulating hormones. / Li, Si Jia; Varga, Károly; Archer, Phillip; Hruby, Victor J; Sharma, Shubh D.; Kesterson, Robert A.; Cone, Roger D.; Kunos, George.

In: Journal of Neuroscience, Vol. 16, No. 16, 15.08.1996, p. 5182-5188.

Research output: Contribution to journalArticle

Li, SJ, Varga, K, Archer, P, Hruby, VJ, Sharma, SD, Kesterson, RA, Cone, RD & Kunos, G 1996, 'Melanocortin antagonists define two distinct pathways of cardiovascular control by α- and γ-melanocyte-stimulating hormones', Journal of Neuroscience, vol. 16, no. 16, pp. 5182-5188.
Li, Si Jia ; Varga, Károly ; Archer, Phillip ; Hruby, Victor J ; Sharma, Shubh D. ; Kesterson, Robert A. ; Cone, Roger D. ; Kunos, George. / Melanocortin antagonists define two distinct pathways of cardiovascular control by α- and γ-melanocyte-stimulating hormones. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 16. pp. 5182-5188.
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