Estradiol attenuates alpha 2-adrenoceptor-mediated inhibition of hypothalamic norepinephrine release.
These studies tested the hypothesis that estradiol facilitates norepinephrine (NE) neurotransmission by modulating alpha 2-adrenoceptor-mediated inhibition of NE release. KCl-induced overflow of 3H from superfused slices preloaded with 3H-NE was Ca2+ dependent. Hypothalamic slices from estradiol-treated rats exposed to a single KCl pulse (S1) had modestly (20%) but significantly elevated NE release when compared to slices from ovariectomized (OVX) rats. Blockade of alpha 2-adrenoceptors by pretreatment with the imidazoline antagonists idazoxan (IDA) and RX821002 (RX) markedly facilitated NE release during S1 in hypothalamic slices from OVX rats; this facilitation was attenuated or absent in slices from estradiol-treated rats. In additional studies slices were stimulated twice, 24 min apart (S1 and S2), for 3 min with 20 mM KCl. In the absence of drug, the amount of 3H-NE released during S2 was always less than the amount released during S1 (i.e., S2:S1 approximately 0.6), regardless of whether slices were from OVX or estradiol-treated females. When 10 microM IDA was applied after S1 and 15 min prior to S2, the S2: S1 ratio increased to 1.8 +/- 0.1 in hypothalamic slices from OVX animals. In contrast, the S2:S1 ratio rose only to 1.1 +/- 0.2 in slices from estradiol-treated animals. RX applied before S2 markedly increased the S2:S1 ratio in both hypothalamic and preoptic area slices from OVX rats but failed to increase the S2:S1 ratio in slices from estradiol-treated rats. Interestingly, the modest effects of alkaloid alpha 2-antagonists such as yohimbine and rauwolscine on NE release in hypothalamic and preoptic area slices were not modified by estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)
Karkanias
G B
GB
Department of Psychiatry, Albert Einstein College of Medicine, Bronx, New York 10461.
Etgen
A M
AM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D019329:Idazoxan / Q000031:analogs & derivatives; D009638:Norepinephrine / Q000378:metabolism*; D010052:Ovariectomy; D011189:Potassium Chloride / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D004958:Estradiol; D011189:Potassium Chloride; C058525:2-methoxyidazoxan; D002118:Calcium; D009638:Norepinephrine; D019329:Idazoxan