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P2X7 Receptors Mediate Hormone Release in nerve terminals of the Neurohypophysis (NH)
Author(s) -
Cuadra Adolfo Ernesto,
Custer Edward,
Bosworth Elizabeth,
Raizada Mohan K.,
Lemos Jose R
Publication year - 2013
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.27.1_supplement.935.8
Subject(s) - agonist , antagonist , divalent , endocrinology , medicine , chemistry , receptor , population , hypothalamus , hormone , patch clamp , biology , environmental health , organic chemistry
P2X7R expression in neurons is controversial; however, studies suggest that it may play a role in hormone release in the hypothalamic NH system (HNS). We examined this in isolated NH terminals (NHT). Application of the P2X7R agonist, BzATP, to NHT resulted in increased levels of sustained AVP release, compared with ATP. Further experiments showed that the sustained release was inhibited by the P2X7R antagonist brilliant blue‐G (BBG). Confocal microscopy showed P2X7R‐immunoreactivity (IR) in slice sections and in isolated terminals of the NH. However, the cell bodies in the hypothalamus that project to the NH were devoid of P2X7R‐IR. Patch clamp studies revealed that subpopulations of NHT displayed differential sensitivity to ATP in evoking ion currents. One population showed a pEC50 of 5.2 ± 0.1 M and the second showed a pEC50 of 3.9 ± 0.2 M (T‐test, p< 0.0002, n=5–6), the latter being consistent with P2X7R. In low divalent cationic media the BzATP, gave a pEC50 of 5.6 ± 0.15 and pretreatment with 10 and 300 nM BBG inhibited currents by 51.8 ± 13.1 and 12.3 ± 4.2 percent of control, respectively (1 way ANOVA, P < 0.0001, n=5). The poor sensitivity to ATP and the marked inhibition of BzATP‐mediated current by BBG are hallmarks of P2X7R function. These results lead us to conclude that P2X7R is present in NHT and play a functional role in hormone release in the HNS. (Study supported by NIH grant NS29470 to JRL)