Characterization of purinergic P2X 4 receptor channels expressed in anterior pituitary cells

• Published in: American journal of physiology: endocrinology and metabolism Vol. 298; no. 3; pp. E644 - E651
• Main Authors: Zemkova, Hana, Kucka, Marek, Li, Shuo, Gonzalez-Iglesias, Arturo E., Tomic, Melanija, Stojilkovic, Stanko S.
• Format: Journal Article
• Language: English
• Published: 01.03.2010
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00558.2009

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.