Effects of alpha-methyldopa and its metabolites on prolactin release: in vivo and in vitro studies
Wiggins, J.F.; Sved, A.F.; Fernstrom, J.D.
Journal of Pharmacology and Experimental Therapeutics 212(2): 304-308
1980
ISSN/ISBN: 0022-3565 PMID: 6766188 Document Number: 161157
The injection of .alpha.-methyldopa (MD) rapidly increased serum prolactin (PRL) levels in male rats. Serum hormone levels plateaued within 15 min of MD injection; the minimal effective dose of MD was 25 mg/kg. In vitro experiments with rat hemipituitaries were conducted to explore whether MD or 1 of its major metabolites might directly stimulate PRL secretion. Incubation with MD (2.8 .times. 10-5 M) failed to modify PRL release into the medium; incubation of hemipituitaries with .alpha.-methyldopamine (2.9 .times. 10-5 M), .alpha.-methylnorepinephrine (2.7 .times. 10-5 M), or 3-O-methyldopa (2.7 .times. 10-4 M) reduced PRL secretion. Incubation with 3-O-methyl-.alpha.-methyldopamine (2.8 .times. 10-5 M) or 3-O-methyl-.alpha.-methylnorepinephrine (2.6 .times. 10-5 M) did not affect PRL release. Incubation with MD (2.8 .times. 10-5 M) did not block the inhibition of PRL release by dopamine (3.2 .times. 10-7 M). Several MD metabolites were administered to male rats to determine whether in vitro effects could be duplicated in vivo. The injection of .alpha.-methyldopamine or .alpha.-methylnorepinephrine (25 mg/kg) decreased serum PRL levels; injection of 3-O-methyl-.alpha.-methyldopa, 3-O-methyl-.alpha.-methyldopamine or 3-O-methyl-.alpha.-norepinephrine (each at 25 mg/kg) had no effect. MD or any of its metabolites did not elevate serum PRL levels by directly stimulating the pituitary. MD does not act as a dopamine antagonist at the pituitary. MD probably acts within the brain to influence the hypothalamic release of a pituitary trophic or inhibitory hormone.