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ATP elicits inward currents in isolated vasopressinergic neurohypophysial terminals via P2X2 and P2X3 receptors

  • Cell and Molecular Physiology
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Abstract

Effects of extracellular adenosine tri-phosphate (ATP) on ionic currents were investigated using the perforated-patch whole-cell recording technique on isolated terminals of the Hypothalamic Neurohypophysial System (HNS). ATP induced a current response in 70% of these isolated terminals. This inwardly-rectifying, inactivating current had an apparent reversal near 0 mV and was dose-dependent on ATP with an EC50=9.6±1.0 μM. In addition, current amplitudes measured at maximal ATP concentrations and optimum holding potentials had a current density of 70.8 pA pF−1 and were greatly inhibited by suramin and PPADS. Different purinergic receptor agonists were tested, with the following efficacy: ATP ≥ 2-methylthioATP > ATP-γ-S > Bz-Bz-ATP > α,β-methylene-ATP > β,γ-methylene-ATP. However, UTP and ADP were ineffective. These data suggest the involvement of a P2X purinergic receptor in the ATP-induced responses. Immunocytochemical labeling in vasopressinergic terminals indicates the existence of P2X2,3,4, and 7, but not P2X6 receptors. Additionally, P2X2 and 3 were not found in terminals which labeled for oxytocin. In summary, the EC50, decay, inactivation, and pharmacology indicate that a functional mixture of P2X2 and 3 homomeric receptors mediate the majority of the ATP responses in vasopressinergic HNS terminals. We speculate that the characteristics of these types of receptors reflect the function of co-released ATP in the terminal compartment of these and other CNS neurons.

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Acknowledgements

This work was supported by NIH grant NS29470. Thanks to Nicolas Hussy for helpful discussions and Catherine Wanko for technical assistance.

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Correspondence to José R. Lemos.

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Knott, T.K., Velázquez-Marrero, C. & Lemos, J.R. ATP elicits inward currents in isolated vasopressinergic neurohypophysial terminals via P2X2 and P2X3 receptors. Pflugers Arch - Eur J Physiol 450, 381–389 (2005). https://doi.org/10.1007/s00424-005-1471-x

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