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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
Author(s) -
Welman A. D.,
Daya S.
Publication year - 1990
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490260115
Subject(s) - melatonin , pineal gland , agonist , endocrinology , medicine , alpha (finance) , methyldopa , serotonin , adrenergic receptor , chemistry , receptor , pharmacology , biology , construct validity , nursing , blood pressure , patient satisfaction
Abstract 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 or 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. Thse 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 eveidence 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.