Central noradrenergic neurons signal via ATP to elicit vasopressin responses to haemorrhage

Abstract

It is now clear that ATP acts as a neurotransmitter in both the peripheral and central nervous systems. In the periphery, purinergic transmission has been best studied at certain sympathetic neuroeffector junctions where ATP, co-localized with noradrenaline, is used to elicit the primary post-junctional response. More recently, several groups have raised the possibility that central catecholaminergic neurons might use ATP in a similar fashion. Accordingly, we now present findings from immediate early gene expression and electrophysiological studies which indicate that ATP, acting through P2 purinoreceptors, is used as a transmitter by caudal brainstem noradrenergic neurons, the A1 group, in their interaction with vasopressinergic neurosecretory cells. Supraoptic nucleus vasopressin cell responses to moderate haemorrhage, known to be generated by the A1 projection, were suppressed by hypothalamic application of the P2 receptor antagonist suramin. However, suramin did not alter vasopressin cell responses to osmotic challenge or severely hypotensive haemorrhage, two stimuli known to excite vasopressin cells independently of the A1 projection. These data are consistent with an identity of action between the A1 input to vasopressin cells and the activation of ATP receptors on vasopressin cells. The use of ATP as a transmitter by other catecholamine neurons in the brain awaits further confirmation, but the present findings suggest that in certain instances the therapeutic manipulation of central catecholamine neuron output might best be achieved with pharmacological agents which target purinergic rather than adrenergic transmission.