P2X7 Receptors in Neurohypophysial Terminals: Evidence for their Role in Arginine‐Vasopressin Secretion

Abstract

Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular function and related pathologies. The mechanism involved in its release into the circulation is complex and highly regulated. Recent work has implicated the purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R action in this endocrine system and whether or not it directly mediates release in secretory neurons have not been determined. We hypothesized that the P2X7R is expressed and mediates AVP release in NH terminals. P2X7R function was first examined by patch-clamp recordings in isolated NH terminals. Results revealed that subpopulations of isolated terminals displayed either high ATP-sensitivity or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R. Additional recordings showed that terminals showing sensitivity to the P2X7R-selective agonist, BzATP, were further inhibited by P2X7R selective antagonists, AZ10606120 and brilliant blue-G. In confocal micrographs from isolated terminals of the NH showed that P2X7R-immunoreactivity was localized in the plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our results showed that BzATP evoked sustained AVP release in NH terminals, which was inhibited by AZ10606120. Taken together, our data lead us to conclude that the P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.

Mechanism of P2X7 receptor-dependent enhancement of neuromuscular transmission in pannexin 1 knockout mice

“…In addition to our data, the ability of BzATP as P2X7 receptor agonist to modulate neurotransmitter release was demonstrated in central and peripheral synapses, where the direct activation of presynaptic P2X7 receptors by BzATP was suggested [11,[33][34][35][36][37]. However, the presence of presynaptic P2X7 receptors at nerve terminals has been recently challenged and presynaptic effects of BzATP were considered as a result of activation of glial rather than neuronal P2X7 receptors, followed by release of gliotransmitters [38].…”

Purinergic receptor types in the hypothalamic‐neurohypophysial system

“…OT-NH terminals demonstrate increased responses to the P2X7R selective agonist Benzyl-ATP (BzATP) when compared to equivalent doses of ATP (6). In agreement with the electrophysiological results, P2X2 receptors specifically regulate AVP release (19), while OT release appears to be regulated by P2X7 receptors (5). In contrast, activation of adenosine receptors inhibits release of both neuropeptides (44).…”

“…ATP stimulation of identified (8) rat AVP-neurohypophysial (NH) terminals (NHT) generate currents with an EC 50 of ~10 μM (17, 20). In contrast, dose-response data show that OT terminals have a much lower sensitivity (EC 50 of >100 μM) to ATP (5) than AVP terminals. OT-NH terminals demonstrate increased responses to the P2X7R selective agonist Benzyl-ATP (BzATP) when compared to equivalent doses of ATP (6).…”

“…We have also examined P2X7R localization (5), by using a stereo-specific ecto-P2X7 antibody. While the SON and PVN contain its mRNA (37) and show P2X7R immunoreactivity (IR), the receptor is absent from membranes of magnocellular neurons.…”

Quantifying Ca2+ Current and Permeability in ATP-gated P2X7 Receptors

“…Although the presence of P2X7Rs on central neu-rons is controversial (6,40), recent data suggest they play a role in modulation of release of transmitters and hormones (41,42). For example, ATP-gated Ca 2ϩ influx through presynaptic P2X7Rs triggers glutamate release from cortical synaptosomes (43,44), GABA release from hippocampal slices (45), and arginine-vasopressin release from neurohypophysial terminals (46).…”