Synergistic activation of astrocytes by ATP and norepinephrine in the rat supraoptic nucleus

Supraoptic nucleus (SON) neurons receive a dense innervation from noradrenergic fibers, the activity of which stimulates vasopressin (VP) and oxytocin (OT) release, notably during homeostatic regulation of blood pressure and volume. This regulation is known to involve the co-release of norepinephrine (NE) and ATP, which act in synergy to stimulate Ca2+ increase in SON neurons and to enhance release of VP and OT from hypothalamo-neurohypophysial explants. We here demonstrate that both ATP and NE also trigger transient intracellular Ca2+ rise in rat SON astrocytes, the two agonists showing a synergistic action similarly to what has been reported in SON neurons. The responses to both agonists are not or are only moderately affected after blockade of neuronal activity by tetrodotoxin, or of neurotransmitter release by removal of extracellular Ca2+, suggesting that the receptors involved are located on the astrocytes themselves. ATP acts via P2Y1 receptors, as indicated by the pharmacological profile of Ca2+ responses and the strong immunolabeling for this receptor in SON astrocytes. Responses to NE involve both α and β adrenergic receptors, the latter showing a permissive role on the former. These results point to further implication of SON astrocytes in the regulation of VP and OT secretion, and suggest that they are potentially important elements participating in all regulatory processes of hypothalamo-neurohypophysial function that involve activation of noradrenergic pathways.