α1‐Adrenergic receptor (α1‐AR) subtypes: Involvement in regulation of supraoptic nucleus (SON) vasopressin (VP) and oxytocin (OT) neurons

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.