EVIDENCE FOR A ROLE OF PITUITARY ATP RECEPTORS IN THE REGULATION OF PITUITARY-FUNCTION

Despite a rapidly increasing acceptance for a role of ATP as an extrac ellular mediator in several biological systems, the present report sho ws 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 ha ve coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP a nd UTP (100 mu M) caused a >14-fold increase in the rate of luteinizin g hormone release from superfused cells. Adenosine 5'-[alpha,beta-meth ylene]triphosphate and 5'-[beta,gamma-methylene]triphosphate were inef fective, and 2-methylthio-ATP had only a modest stimulatory effect. Ho mologous and heterologous desensitization occurred with UTP and ATP, a nd these did not have additive effects. Thus, nucleotides can be effec tive stimulators of luteinizing hormone release through a single class of ATP receptor (P-2U subtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a conc entration- and Ca2+-dependent manner, which was desensitized by pretre atment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary c ells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary-in particular, in gonadotrope-function.