Evidence for a Role of Pituitary ATP Receptors in the Regulation of Pituitary Function

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-05, Vol.92 (11), p.5219-5223
• Main Authors: Chen, Zhen-Ping, Kratzmeier, Martin, Levy, Andrew, McArdle, Craig A., Poch, Annette, Day, Andrew, Mukhopadhyay, Amal K., Lightman, Stafford L.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; B lymphocytes; Calcimycin - pharmacology; Cell culture techniques; Cell lines; Cells, Cultured; Cellular biology; Chromaffin cells; Cultured cells; Dose-Response Relationship, Drug; Endocrine system; Female; Gonadotropin-Releasing Hormone - pharmacology; Hormones; Inurement; Kinetics; Luminescent Measurements; Luteinizing Hormone - metabolism; Mast cells; Nucleosides - pharmacology; Nucleotides; Pituitary Gland - metabolism; Pituitary Gland - physiology; Rats; Rats, Wistar; Receptors; Receptors, Purinergic P2 - physiology; Ribonucleotides - pharmacology; Rodents; Time Factors; Uridine Triphosphate - pharmacology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.11.5219

Despite a rapidly increasing acceptance for a role of ATP as an extracellular mediator in several biological systems, the present report shows that ATP may mediate physiological responses in pituitary cells. We have now been able to demonstrate a specific action of ATP receptors to mediate the release of luteinizing hormone from gonadotropes and have coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP and UTP (100 μM) caused a >14-fold increase in the rate of luteinizing hormone release from superfused cells. Adenosine 5'-α,β-methylene]triphosphate and 5'-[β,γ-methylene triphosphate were ineffective, and 2-methylthio-ATP had only a modest stimulatory effect. Homologous and heterologous desensitization occurred with UTP and ATP, and these did not have additive effects. Thus, nucleotides can be effective stimulators of luteinizing hormone release through a single class of ATP receptor (P2Usubtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a concentration- and Ca2+-dependent manner, which was desensitized by pretreatment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary cells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary-in particular, in gonadotrope-function.