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Locally synthesized angiotensin modulates pineal melatonin generation
Ovidiu Baltatu1, Solange Castro Afeche, Sabrina Heloisa José dos Santos
1Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany. baltatu@mdc-berlin.de
Journal of Neurochemistry
|March 21, 2002
Summary
The renin-angiotensin system (RAS) locally regulates pineal melatonin production by influencing tryptophan hydroxylase (TPH) activity via AT1 receptors. This study reveals a key mechanism in indole synthesis modulation.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Pharmacology
Background:
- The renin-angiotensin system (RAS) is known for its systemic roles in blood pressure regulation.
- Its influence on pineal gland function, specifically melatonin production, is less understood.
- Melatonin, a key pineal hormone, regulates circadian rhythms and has antioxidant properties.
Purpose of the Study:
- To investigate the mechanisms by which the RAS influences pineal melatonin production.
- To determine the significance of this interaction for indole synthesis.
- To elucidate the role of AT1 receptors in mediating RAS effects on the pineal gland.
Main Methods:
- High-performance liquid chromatography (HPLC) with electrochemical detection was used to quantify pineal melatonin and indoles.
- Angiotensin AT1-receptor blockade was performed using Losartan in vivo and in cultured pineal glands.
- N-acetyltransferase (NAT) activity was measured radiometrically.
- Transgenic rats with inhibited angiotensinogen production in astrocytes (TGR(ASrAOGEN)) were used to assess in vivo relevance.
- Tryptophan hydroxylase (TPH) and NAT mRNA levels were quantified by real-time RT-PCR.
Main Results:
- AT1-receptor blockade with Losartan significantly decreased pineal melatonin content by 35% in vivo and 32.4% in vitro.
- In TGR(ASrAOGEN) rats, pineal melatonin was reduced by 17.5%, indicating local RAS involvement.
- Losartan treatment reduced pineal levels of 5-hydroxytryptophan, serotonin, and N-acetylserotonin, suggesting decreased TPH activity.
- TPH mRNA levels were significantly lower in TGR(ASrAOGEN) rats compared to controls.
- NAT activity and expression remained unaffected by RAS modulation.
Conclusions:
- A local pineal RAS tonically modulates indole synthesis.
- This modulation occurs via AT1 receptors and influences the activity of tryptophan hydroxylase (TPH).
- The findings highlight a novel regulatory pathway for pineal function involving the RAS.