Characterization of purinergic P2X4 receptor channels expressed in anterior pituitary cells

Anterior pituitary cells express cation-conducting P2X receptor channels (P2XRs), but their molecular identity, electrophysiological properties, cell-specific expression pattern, and physiological roles have been only partially characterized. In this study, we show by quantitative RT-PCR that mRNA t...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2010-03, Vol.298 (3), p.E644-E651
Main Authors: Zemkova, Hana, Kucka, Marek, Li, Shuo, Gonzalez-Iglesias, Arturo E, Tomic, Melanija, Stojilkovic, Stanko S
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Cells, Cultured
Female
Ion Channel Gating - physiology
Membrane Potentials - physiology
Pituitary Gland - cytology
Pituitary Gland - physiology
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X4
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Summary:Anterior pituitary cells express cation-conducting P2X receptor channels (P2XRs), but their molecular identity, electrophysiological properties, cell-specific expression pattern, and physiological roles have been only partially characterized. In this study, we show by quantitative RT-PCR that mRNA transcripts for the P2X(4) subunit are the most abundant in rat anterior pituitary tissue and confirm the P2X(4)R protein expression by Western blot analysis. Single-cell patch-clamp recordings show that extracellular ATP induced an inward depolarizing current in a majority of thyrotropin-releasing hormone-responsive pituitary cells, which resembled the current profile generated by recombinant P2X(4)R. The channels were activated and desensitized in a dose-dependent manner and deactivated rapidly. Activation of these channels led to stimulation of electrical activity and promotion of voltage-gated and voltage-insensitive Ca(2+) influx. In the presence of ivermectin, a specific allosteric modulator of P2X(4)Rs, there was an approximately fourfold increase in the maximum amplitude of the ATP-induced inward current, accompanied by an increase in the sensitivity of receptors for ATP, slowed deactivation of receptors, and enhanced ATP-induced prolactin release. These results indicate that thyrotropin-releasing hormone-responsive cells, including lactotrophs, express homomeric and/or heteromeric P2X(4)Rs, which facilitate Ca(2+) influx and hormone secretion.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00558.2009