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α1‐Adrenergic receptor (α1‐AR) subtypes: Involvement in regulation of supraoptic nucleus (SON) vasopressin (VP) and oxytocin (OT) neurons
Author(s) -
Sladek Celia D.,
Stevens Wanida,
Song Zhilin
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.993.5
Subject(s) - oxytocin , supraoptic nucleus , phenylephrine , endocrinology , medicine , vasopressin , agonist , chemistry , intracellular , secretion , receptor , biology , biochemistry , blood pressure
Noradrenergic pathways (that co‐release ATP) transmit cardiovascular and suckling information to stimulate VP and OT secretion. Both ATP and phenylephrine (PE, α1‐AR agonist) increase intracellular calcium ([Ca ++ ]i) in SON neurons and induce transient VP/OT release from explants of the hypothalamo‐neurohypophyseal sysem (HNS). Simultaneous exposure to ATP+PE induces a synergistic increase in VP/OT release that is sustained for hours. SON neurons express several α1AR subtypes (α1A, α1B, and α1D). Antagonists of these subtypes were used to evaluate their respective roles in inducing Ca ++ and VP/OT responses to PE and ATP+PE. Live cell Ca ++ imaging studies were performed in Fura‐2 loaded HNS explants. VP/OT release from perifused HNS explants was measured using radioimmunoassay. Antagonists of α1A‐ARs [WB4101 (100 μM) and 5‐methylurapidil (1 μM)] prevented PE‐induced increases in [Ca ++ ]i, and attenuated the response to ATP+PE. Neither α1B‐AR (AH11110A, 100 nM) nor α1D‐AR antagonists (BMY7378, 10 nM) affected the Ca ++ response to PE. However, neither WB4101 nor AH11110A altered VP/OT release induced by exposure to ATP+PE. These findings demonstrate functional expression of α1A‐ARs in SON neurons, and indicate that PE‐induced increases in [Ca ++ ]i are primarily mediated by α1A‐ARs. However, additional α1‐AR subtypes participate in the sustained response to ATP+PE. Supported by NIH RO1‐NS29759.