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Characterization of Purinergic Receptors and Receptor-Channels Expressed in Anterior Pituitary Cells

Taka-aki Koshimizu, Melanija Tomi, Anderson On-Lam Wong, Dragoslava Zivadinovic and Stanko S. Stojilkovic

Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-4510

Address all correspondence and requests for reprints to: Dr. Stanko Stojilkovic, Section on Cellular Signaling, ERRB/NICHD, Building 49, Room 6A-36, 49 Convent Drive, Bethesda, Maryland 20892-4510. E-mail: stankos{at}helix.nih.gov

Purinergic G protein-coupled receptors (P2YR) and ion-conducting receptor-channels (P2XR) are present in the pituitary. However, their identification, expression within pituitary cell subpopulations, and the ability to elevate intracellular Ca²⁺ concentration ([Ca²⁺]_i) in response to ATP stimulation were incompletely characterized. Here we show that mixed populations of rat anterior pituitary cells express messenger RNA transcripts for P2Y₂R, P2X_2aR, P2X_2bR, P2X₃R, P2X₄R, and P2X₇R. The transcripts and functional P2Y₂R were identified in lactotrophs and GH3 cells, but not in somatotrophs and gonadotrophs, and their activation by ATP led to an extracellular Ca²⁺-independent rise in [Ca²⁺]_i in about 40% of cells tested. Lactotrophs and GH3 cells, but not somatotrophs, also express transcripts for P2X₇R, P2X₃R, and P2X₄R. Functional P2X₇R were identified in 74% of lactotrophs, whereas 50% of these cells expressed P2X₃R and 33% expressed P2X₄R. Coexpression of these receptor subtypes in single lactotrophs was frequently observed. Purified somatotrophs expressed transcripts for P2X_2aR and P2X_2bR, and functional receptors were identified in somatotrophs and gonadotrophs, but not in lactotrophs. Consistent with the cell-specific expression of transcripts for P2X₂R and P2X₃R, the expression of their functional heteromers was not evident in pituitary cells. Receptors differed in their capacities to elevate and sustain Ca²⁺ influx-dependent rise in [Ca²⁺]_i during the prolonged ATP stimulation. These results indicate that the purinergic system of anterior pituitary is extremely complex and provides an effective mechanism for generating a cell- and receptor-specific Ca²⁺ signaling pattern in response to a common agonist.

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