| Autor: |
Kim, M. S, Small, C. J, Russell, S. H, Morgan, D. G. A, Abbott, C. R, AlAhmed, S. H, Hay, D. L, Ghatei, M. A, Smith, D. M, Bloom, S. R |
| Předmět: |
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| Zdroj: |
Journal of Neuroendocrinology; Apr2002, Vol. 14 Issue 4, p276-282, 7p, 8 Graphs |
| Abstrakt: |
Abstract The hypothalamic melanocortin system is important in the central regulation of food intake and body weight. We have previously demonstrated that intracerebroventricular administration of α-melanocyte stimulating hormone (α-MSH), a nonselective MC3 and MC4 receptor agonist, stimulated plasma thyroid-stimulating hormone, and agouti-related protein (AgRP), an MC3 and MC4 receptor antagonist, suppressed it. In this study, we investigated the effects of MC3 and MC4 receptor (MC3-R and MC4-R) selective agonists and antagonists on the release of thyrotropin-releasing hormone (TRH) from hypothalamic explants in vitro . α-MSH stimulated TRH release from the rat hypothalamic explants (α-MSH 100 nM 230 ± 22.9% basal, P < 0.005). In contrast, γ2 -MSH, a selective MC3-R agonist, suppressed TRH release (γ2 -MSH 10 µM 76.2 ± 7.4% basal, P < 0.05). AgRP (83-132), a nonselective MC3/4-R antagonist, induced no change in TRH release whilst JKC-363 (cyclic [Mpr11 , D-Nal14 , Cys18 , Asp22 -NH2 ]-β-MSH 11-22), a selective MC4-R antagonist, suppressed it (JKC-363 10 nM 57.2 ± 11.5% basal, P < 0.05). Both AgRP (83-132) and JKC-363 blocked α-MSH stimulated TRH release but only AgRP (83-132) blocked the inhibitory effect of γ2 -MSH on TRH release. These data suggest differential roles for the MC3 and MC4 receptors in TRH release; MC3-R agonism inhibiting and MC4-R agonism stimulating TRH release. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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