Contrasting data have been reported so far on the role played by γ-aminobutyric acid (GABA) in the control of PRL secretion in the rat. Based on the findings that systemic administration of muscimol (M), a powerful agonist at GABA receptors, lowered plasma PRL in male rats, studies were undertaken to determine both the mechanism(s) of M-induced inhibition of plasma PRL and the reason(s) for the disparity between data pointing to a stimulatory and those favoring an inhibitory role of GABA on PRL secretion. In freely behaving male rats, administration of either picrotoxin (PICRO; 1 mg/kg, iv) or bicuculline (BIC; 0.4 mg/kg, iv), two GABA antagonist drugs, failed to counteract and instead potentiated the PRL-lowering effect of M (2.0 mg/kg, iv). BIC alone decreased baseline PRL levels. In ovariectomized estrogen-primed rats, PICRO and BIC, at the same doses, elicited a striking decline of the elevated basal PRL levels and were again unable to oppose the effect of M. In contrast to its effect after systemic injection, M (500 ng) injected into the lateral ventricle of freely behaving male rats elicited a clear-cut rise in plasma PRL which was suppressed by BIC. The dual effect of M on PRL secretion according to the route of administration was indicative of an extra-central nervous system site of action of the drug when given systemically. In keeping with this hypothesis, M (2.5x10 -5 M) inhibited PRL release from rat isolated anterior pituitaries (AP), an effect which was abolished by coincubation with equimolar doses of PICRO; however, M (2 mg/kg, iv) failed to lower plasma PRL levels in hypophysectomized rats bearing an ectopic AP. Also favoring a direct AP site of action for M was the observation that it completely abolished, after systemic administration (2 mg/kg, iv), the striking rise in plasma PRL exerted by α-methylparatyrosine, a drug which acts at the central nervous system level. Collectively, these data would demonstrate the existence of a dual GABAergic control of PRL secretion, one stimulatory, exerted through the central nervous system, and the other inhibitory, occuring at the level of the AP.
|Titolo:||DUAL GAMMA-AMINOBUTYRIC ACID CONTROL OF PROLACTIN SECRETION IN THE RAT|
RACAGNI, GIORGIO ANGELO (Penultimo)
MULLER, EUGENIO (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1979|
|Digital Object Identifier (DOI):||10.1210/endo-105-3-778|
|Appare nelle tipologie:||01 - Articolo su periodico|