Role of nucleotide P2 receptors in calcium signaling and prolactin release in pituitary lactotrophs.
Anterior pituitary cells express nucleotide-gated G protein-coupled P2 receptors (P2YRs) and cation-conducting channels (P2XRs). However, the identification of P2 receptors subtypes and their native ligands, and the distribution and function of these receptors within the secretory and non-secretory pituitary cells has been incompletely characterized. The focus in this study was on lactotroph subpopulation of cells. ATP and ADP, but not UTP and UDP, triggered calcium signaling in a majority (85%) of lactotrophs and prolactin release in mixed pituitary cells. Consistent with the role of P2 receptors in signaling and secretion, the actions of ATP and ADP were abolished in the presence of apyrase, an ectonucleotidase. Transcripts for Gq-coupled calcium-mobilizing P2Y1R, P2Y2R, P2Y4R, and P2Y6R, as well as Gi-coupled P2Y12R, were identified in mixed anterior pituitary cells. The ligand-selectivity profile of calcium mobilization-dependent signaling and prolactin secretion and the blockade of these responses by pyridoxal 5-phosphate 6-azophenyl-2',4'-disulphonic acid indicated that P2Y1R mediates the stimulatory action of ATP and ADP. Within the channels expressed in anterior pituitary (P2X2R, P2X3R, P2X4R, and P2X7R), the P2X4R subtype provides a major pathway for calcium influx-dependent signaling and prolactin secretion. This conclusion was based on comparison of native to recombinant channels with respect to their ligand preference, sensitivity to pyridoxal 5-phosphate 6-azophenyl-2',4'-disulphonic acid, and the rates of calcium signal desensitization.
He
Mu-Lan
ML
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892-4510, USA.
Gonzalez-Iglesias
Arturo E
AE
Stojilkovic
Stanko S
SS
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D005260:Female; D008024:Ligands; D010903:Pituitary Gland, Anterior / Q000166:cytology*; D011388:Prolactin / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058848:Receptors, Purinergic P2X4; D058472:Receptors, Purinergic P2Y1
D008024:Ligands; C548226:P2RX4 protein, human; C546382:P2RY1 protein, human; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058472:Receptors, Purinergic P2Y1; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011388:Prolactin