title: Spontaneous and agonist-induced calcium oscillations in single human nonfunctioning adenoma cells.
abstract: The effects of gonadotropin-releasing hormone (GnRH) and GnRH-associated peptide (GAP) on cytosolic free calcium concentration ([Ca(2+)](i)) were investigated in 20 human nonfunctioning pituitary adenomas. We divided these tumors into three classes according to their response pattern to hypothalamic peptides. In type I adenomas (8 out of 20 adenomas), GnRH and GAP mobilized intracellular calcium ions stored in a thapsigargin (TG)-sensitive store. For the same concentration of agonist, two distinct patterns of GnRH-GAP-induced Ca(2+) mobilization were observed (1) sinusoidal oscillations, and (2) monophasic transient. The latter is followed by a protein kinase C (PKC)-dependent increase in calcium influx through L-type channels. In type II adenomas (7 out of 20 adenomas), GnRH and GAP only stimulate calcium influx through dihydropyridine-sensitive Ca(2+) channels by a PKC-dependent mechanism. TG (1 μM) did not affect [Ca(2+)](i) in these cells, suggesting that they do not possess TG-sensitive Ca(2+) pools. All the effects of GnRH and GAP were blocked by an inhibitor of phospholipase C (PLC), suggesting that they were owing to the activation of the phosphoinositide turnover. Type I and type II adenoma cells showed spontaneous Ca(2+) oscillations that were blocked by dihydropyridines and inhibition of PKC activity. GnRH and GAP had no effect on the [Ca(2+)](i) of type III adenoma cells that were also characterized by a low resting [Ca(2+)](i) and by the absence of spontaneous Ca(2+) fluctuations. K(+)-induced depolarization provoked a reduced Ca(2+) influx, whereas TG had no effect on the [Ca(2+)](i) of type III adenoma cells. The variety of [Ca(2+)](i) response patterns makes these cells a good cell model for studying calcium homeostasis in pituitary cells.
authors.affiliation: Laboratoire de Neurophysiologie, CNRS URA 1200, Université de Bordeaux 2, 146 rue Léo Saignat, PB 22, 33076, Bordeaux Cédex, France.
authors.forename: P
authors.initials: P
authors.lastname: Vacher
authors.forename: L
authors.initials: L
authors.lastname: Bresson-Bepoldin
authors.forename: L
authors.initials: L
authors.lastname: Dufy-Barbe
authors.forename: M F
authors.initials: MF
authors.lastname: Odessa
authors.forename: J
authors.initials: J
authors.lastname: Guerin
authors.forename: B
authors.initials: B
authors.lastname: Dufy