Regulation of neuropeptide Y release from hypothalamic slices by melanocortin-4 agonists and leptin.
We have examined the regulation of the orexigenic neurotransmitter, NPY, in hypothalamic slices of rat brain to discover whether the leptin or melanocortin receptor-4 (MCR-4) agonists, which act as satiety signals, can influence the release of this neurotransmitter. Basal and potassium-stimulated NPY release from hypothalamic slices was not significantly altered by the addition of recombinant murine leptin. However, the melanocortin-4 agonists, alpha-MSH and MT-II, significantly inhibited potassium-stimulated NPY release (p < 0.01) without significantly altering basal NPY release. However, the MCR-4 antagonist, agouti-related protein, did not significantly alter either basal or stimulated NPY release. In conclusion, hypothalamic NPY release can be attenuated by MCR-4 agonists, but not by leptin, suggesting that the activation of MCR-4 receptors leading to satiety can also further inhibit food intake through an inhibition of orexigenic NPYergic activity.
King
P J
PJ
Diabetes and Endocrinology Research Unit, Department of Medicine, Duncan Building, Daulby Street, Liverpool University, Liverpool, UK. p.j.king@liverpool.ac.uk
Widdowson
P S
PS
Doods
H
H
Williams
G
G
D054369:Agouti-Related Protein; D000818:Animals; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000819:agonists*; D011994:Recombinant Proteins / Q000494:pharmacology; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; D011994:Recombinant Proteins; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D000521:alpha-MSH