Non‐desensitizing purinergic receptors (P2R) are responsible for sustained stimulation of vasopressin (VP) release by ATP and phenylephrine (PE)

Abstract

ATP and norepinephrine (NE) are neurotransmitters carrying cardiovascular information to vasopressin (VP) neurons. Simultaneous exposure of hypothalamo‐neurohypophyseal system explants to ATP and PE (α1‐adrenergic receptor agonist) results in potentiation of VP release characterized by both an increase in the peak response and conversion of a transient response to a response that is sustained for hours. (J. Neurosci. 20:8868, 2000). Since the P2X2/3 and P2X7 subtypes of P2XRs do not desensitize, we hypothesized that these receptors are responsible for the sustained response to ATP. A317491 (300nM, P2X3 and P2X2/3R antag.), or 1uM BBG (P2X7R antag.) added during sustained response to ATP+PE attenuated VP release. These data supported the hypothesis that activation of the non‐desensitizing P2X2/3 and P2X7Rs is required for the sustained elevation of VP release characteristic of ATP+PE synergism. A more rapid effect of BBG suggests a prominent role for P2X7Rs. To determine if continued exposure to ATP or PE is required to sustain elevated hormone release, either ATP or PE was removed after 2hrs exposure to ATP+PE. Continued perifusion with PE alone but not ATP is required to maintain VP release. Since NE has been shown to stimulate ATP release from glia (Gorden et al Nat Neurosci 8:1078, 2005), these findings in conjunction with the ability of the P2X2/3 and P2X7R antagonists to attenuate sustained VP release support the interpretation that continuous exposure to PE is required to maintain P2X2/3 and/or P2X7R function. Supported by NIH RO1‐NS27975.