Allopregnanolone-induced modification of presynaptic basal and K+-induced [3H]-norepinephrine efflux from rat cortical slices during the estrous cycle.
Superfused frontal slices of cerebral cortex were preloaded with [3H]-norepinephrine ([3H]NE). Basal [3H]NE efflux and K+-induced [3H]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [3H]NE efflux showed estrous cycle-related variations, with lowest values found during estrus and diestrus II. Allopregnanolone (10(-9) M) potentiated basal [3H]NE efflux from the 1st minute of its application; the effect of the steroid was still present after 20 min. This effect was also dependent upon the estrous cycle, since basal [3H]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [3H]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10(-6) M), the effect of allopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10(-9) M) potentiated the K+-induced [3H]NE release during estrus, but pregnenolone (10(-9) M) was ineffective, suggesting specificity of the neurosteroid. Yohimbine (10(-6) M) also potentiated K+-induced [3H]NE release. When applied simultaneously with allopregnanolone (10(-9) M), a potentiating effect on [3H]NE release was observed. The present results suggest that allopregnanolone is a neurosteroid able to modulate norepinephrine release in the cerebral cortex in an estrous cycle-dependent manner, and that the effect could involve noradrenergic alpha-2 receptors.
Laboratory of Biochemical Pharmacology, P. Catholic University of Chile, University of Santiago, Chile.
J
J
Belmar
C
C
Cuellar
I
I
Llona
S
S
Arancibia
C
C
Kusch
L
L
Tapia-Arancibia
A
A
Pinter
H
H
Pérez
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism*; D004347:Drug Interactions; D004971:Estrus / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry / Q000378:metabolism; D007536:Isomerism; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D011284:Pregnenolone / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D014316:Tritium; D015016:Yohimbine; D011284:Pregnenolone; D011280:Pregnanolone; D011188:Potassium; D009638:Norepinephrine