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An Interaction of Oxytocin Receptors with Metabotropic Glutamate Receptors in Hypothalamic Astrocytes
Author(s) -
Kuo J.,
Hariri O. R.,
Micevych P.
Publication year - 2009
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2009.01922.x
Subject(s) - oxytocin , medicine , endocrinology , metabotropic glutamate receptor , oxytocin receptor , agonist , receptor , metabotropic receptor , glutamate receptor , hypothalamus , chemistry , biology
Hypothalamic astrocytes play a critical role in the regulation and support of many different neuroendocrine events, and are affected by oestradiol. Both nuclear and membrane oestrogen receptors (ERs) are expressed in astrocytes. Upon oestradiol activation, membrane‐associated ER signals through the type 1a metabotropic glutamate receptor (mGluR1a) to induce an increase of free cytoplasmic calcium concentration ([Ca 2+ ] i ). Because the expression of oxytocin receptors (OTRs) is modulated by oestradiol, we tested whether oestradiol also influences oxytocin signalling. Oxytocin at 1, 10, and 100 n m induced a [Ca 2+ ] i flux measured as a change in relative fluorescence [ΔF Ca 2+ = 330 ± 17 relative fluorescent units (RFU), ΔF Ca 2+ = 331 ± 22 RFU, and ΔF Ca 2+ = 347 ± 13 RFU, respectively] in primary cultures of female post‐pubertal hypothalamic astrocytes. Interestingly, OTRs interacted with mGluRs. The mGluR1a antagonist, LY 367385 (20 n m ), blocked the oxytocin (1 n m )‐induced [Ca 2+ ] i flux (ΔF Ca 2+ = 344 ± 19 versus 127 ± 11 RFU, P < 0.001). Conversely, the mGluR1a receptor agonist, (RS)‐3,5‐dihydroxyphenyl‐glycine (100 n m ), increased the oxytocin (1 n m )‐induced [Ca 2+ ] i response (ΔF Ca 2+ = 670 ± 31 RFU) compared to either compound alone (P < 0.001). Because both oxytocin and oestradiol rapidly signal through the mGluR1a, we treated hypothalamic astrocytes sequentially with oxytocin and oestradiol to determine whether stimulation with one hormone affected the subsequent [Ca 2+ ] i response to the second hormone. Oestradiol treatment did not change the subsequent [Ca 2+ ] i flux to oxytocin (P > 0.05) and previous oxytocin exposure did not affect the [Ca 2+ ] i response to oestradiol (P > 0.05). Furthermore, simultaneous oestradiol and oxytocin stimulation failed to yield a synergistic [Ca 2+ ] i response. These results suggest that the OTR signals through the mGluR1a to release Ca 2+ from intracellular stores and rapid, nongenomic oestradiol stimulation does not influence OTR signalling in astrocytes.