Pineal gland as a model to elucidate the primary mode of action of alpha-methyldopa: Alpha-methyldopa induces an increase in the synthesis of N-acetylserotoni and melatonin levels by the rat pineal gland
✍ Scribed by A. D. Welman; S. Daya
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 388 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
An attempt was made to use the pineal gland as a model for the study of the primary mode of action of alpha-methyldopa, which is still unclear. Organ cultures of pineal glands from rats treated chronically with alpha-methyldopa showed enhanced conversion of radio-active serotonin to melatonin (aMT) as well as its precursor, N-acetyl-serotonin (aHT). This treatment was also found to raise serotonin-N-acetyltransferase (NAT) activity. These increases associated with alpha-methyldopa treatment were further enhanced by the beta-adrenergic agonist, isoproterenol, suggesting a supersensitivity-type effect occurring at the level of the beta-receptor. A subsequent binding study, however, showed a decrease in betareceptor binding with exposure to alpha-methyldopa, providing mitigating evidence against the occurrence of a supersensitivity phenomenon. It is possible that a metabolite of alpha-methyldopa acts as an alpha 1 and beta-agonist, resulting in greater melatonin (aMT) and N-acetylserotonin (aHT) synthesis than by a beta-agonist, isoproterenol.