title: Role of the second-messenger cyclic-adenosine 5'-diphosphate-ribose on adrenocorticotropin secretion from pituitary cells.
abstract: We examined the role of the second-messenger cyclic-ADP-ribose (cADPR) on the regulation of ACTH secretion using AtT20 corticotroph tumor cell line. We found that the cADPR antagonist, 8-Br-cADPR, substantially diminished the secretion of ACTH induced by CRH and potassium in these cells, whereas xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, had no effect. In addition, the cADPR agonist, 3-deaza-cADPR, augmented ACTH secretion. The presence of the components of the cADPR system, namely ryanodine receptor, CD38, and cADPR itself, was determined in AtT20 cells. Furthermore, we observed that antagonists of the ryanodine channel and cADPR system can decrease the potassium-induced Ca2+ transients in these cells. These results suggest that cADPR is a second messenger in pituitary cells and regulates ACTH secretion by a mechanism dependent on activation of the ryanodine channel by extracellular Ca2+.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Soares
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.forename: Eduardo N
authors.initials: EN
authors.lastname: Chini
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000032:analysis; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D006706:Homeostasis; D008562:Membrane Glycoproteins; D051379:Mice; D010902:Pituitary Gland / Q000378:metabolism*; D010911:Pituitary Neoplasms; D011188:Potassium / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis; D015290:Second Messenger Systems / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D008562:Membrane Glycoproteins; D019837:Ryanodine Receptor Calcium Release Channel; C402294:cyclic 3-deazaadenosine diphosphoribose; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D051997:ADP-ribosyl Cyclase 1; D011188:Potassium; D002118:Calcium