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N-methyl-D-aspartate (NMDA) stimulates release of alpha-MSH from the rat hypothalamus through release of nitric oxide
C P Wayman1, N V Pike, J F Wilson
1Department of Pharmacology and Therapeutics, University of Wales College of Medicine, Health Park, Cardiff, UK.
Abstract:
Superfusion of rat hypothalamic slices with 10(-4) M N-methyl-D-aspartic acid (NMDA) resulted in increased release of alpha-melanocyte-stimulating hormone (alpha-MSH). Peptide release was blocked by 10(-6) M NG-nitro-L-arginine methyl ester (L-NAME) a specific competitive inhibitor of nitric oxide synthase but not by the inactive enantiomer D-NAME at 10(-6) M. The inhibition by L-NAME was reversed by the addition of 10(-5) mM L-arginine, an excess of enzyme substrate. Release of nitric oxide products into tissue superfusates was stimulated by a 50 mM concentration of potassium ions and by 10(-4) M NMDA. Potassium-stimulated release was blocked by L-NAME. Basal, potassium-stimulated and NMDA-stimulated release of nitric oxide products were significantly inhibited by the NMDA-receptor antagonist D(-)-2-amino-5-phosphopentanoic acid (AP5) at 10(-4) M and by the NMDA-channel blocker ketamine at 10(-4) M. We conclude that nitric oxide mediates the stimulatory action of glutamic acid on the release of alpha-MSH from the rat hypothalamus.
Insights
Nitric oxide (NO) mediates the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from the rat hypothalamus. This process is stimulated by N-methyl-D-aspartic acid (NMDA) and involves NO synthase.
Area of Science:
- Neuroendocrinology
- Neuropharmacology
- Molecular Biology
Background:
- The hypothalamus regulates various physiological functions, including hormone release.
- N-methyl-D-aspartic acid (NMDA) receptors play a crucial role in neurotransmission.
- Nitric oxide (NO) is a signaling molecule implicated in diverse biological processes.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from the rat hypothalamus.
- To determine the involvement of NMDA receptors in NMDA-induced alpha-MSH release.
Main Methods:
- Superfusion of rat hypothalamic slices.
- Measurement of alpha-MSH release.
- Pharmacological inhibition of nitric oxide synthase (NOS) using NG-nitro-L-arginine methyl ester (L-NAME).
- Assessment of NMDA receptor involvement using antagonists like D(-)-2-amino-5-phosphopentanoic acid (AP5) and ketamine.
Main Results:
- N-methyl-D-aspartic acid (NMDA) significantly increased alpha-MSH release.
- The NMDA-induced release of alpha-MSH was blocked by L-NAME, an inhibitor of NO synthase, and this blockade was reversed by L-arginine.
- Potassium ions and NMDA stimulated the release of NO products, which was also inhibited by L-NAME.
- Both NMDA receptor antagonist AP5 and NMDA channel blocker ketamine inhibited basal, potassium-stimulated, and NMDA-stimulated NO product release.
Conclusions:
- Nitric oxide (NO) acts as a mediator in the stimulatory action of glutamic acid (via NMDA receptors) on alpha-MSH release from the rat hypothalamus.
- The findings highlight a novel signaling pathway involving NO in hypothalamic hormone regulation.