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-acetylserotonin and melatonin levels by the rat pineal gland.
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 beta-receptor 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.
Welman
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Department of Biochemistry, Rhodes University, Grahamstown, South Africa.
Daya
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D000818:Animals; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D008750:Methyldopa / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives* / Q000096:biosynthesis
D012701:Serotonin; D008750:Methyldopa; D008550:Melatonin; D007545:Isoproterenol; C006389:N-acetylserotonin