This Article Full Text Full Text (PDF) All Versions of this Article: 20/9/2231    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez-Iglesias, A. E. Articles by Stojilkovic, S. S. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Iglesias, A. E. Articles by Stojilkovic, S. S.

Dependence of Electrical Activity and Calcium Influx-Controlled Prolactin Release on Adenylyl Cyclase Signaling Pathway in Pituitary Lactotrophs

Arturo E. Gonzalez-Iglesias, Yonghua Jiang, Melanija Tomi, Karla Kretschmannova, Silvana A. Andric, Hana Zemkova and Stanko S. Stojilkovic

Section on Cellular Signaling, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland 20892-4510

Address all correspondence and requests for reprints to: Dr. Stanko Stojilkovic, Endocrinology and Reproduction Research Branch/National Institute of Child Health and Human Development/National Institutes of Health, Building 49, Room 6A-36, 49 Convent Drive, Bethesda, Maryland 20892-4510. E-mail: stankos{at}helix.nih.gov.

Pituitary lactotrophs in vitro fire extracellular Ca²⁺-dependent action potentials spontaneously through still unidentified pacemaking channels, and the associated voltage-gated Ca²⁺ influx (VGCI) is sufficient to maintain basal prolactin (PRL) secretion high and steady. Numerous plasma membrane channels have been characterized in these cells, but the mechanism underlying their pacemaking activity is still not known. Here we studied the relevance of cyclic nucleotide signaling pathways in control of pacemaking, VGCI, and PRL release. In mixed anterior pituitary cells, both VGCI-inhibitable and -insensitive adenylyl cyclase (AC) subtypes contributed to the basal cAMP production, and soluble guanylyl cyclase was exclusively responsible for basal cGMP production. Inhibition of basal AC activity, but not soluble guanylyl cyclase activity, reduced PRL release. In contrast, forskolin stimulated cAMP and cGMP production as well as pacemaking, VGCI, and PRL secretion. Elevation in cAMP and cGMP levels by inhibition of phosphodiesterase activity was also accompanied with increased PRL release. The AC inhibitors attenuated forskolin-stimulated cyclic nucleotide production, VGCI, and PRL release. The cell-permeable 8-bromo-cAMP stimulated firing of action potentials and PRL release and rescued hormone secretion in cells with inhibited ACs in an extracellular Ca²⁺-dependent manner, whereas 8-bromo-cGMP and 8-(4-chlorophenyltio)-2'-O-methyl-cAMP were ineffective. Protein kinase A inhibitors did not stop spontaneous and forskolin-stimulated pacemaking, VGCI, and PRL release. These results indicate that cAMP facilitates pacemaking, VGCI, and PRL release in lactotrophs predominantly in a protein kinase A- and Epac cAMP receptor-independent manner.

This article has been cited by other articles:

				S. Constantin and S. Wray Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Hyperpolarization-Activated Cyclic Nucleotide-Modulated Channels but Is Sensitive to Protein Kinase A-Dependent Phosphorylation Endocrinology, July 1, 2008; 149(7): 3500 - 3511. [Abstract] [Full Text] [PDF]

				K. Janssens, M. Boussemaere, S. Wagner, K. Kopka, and C. Denef {beta}1-Adrenoceptors in Rat Anterior Pituitary May Be Constitutively Active. Inverse Agonism of CGP 20712A on Basal 3',5'-Cyclic Adenosine 5'-Monophosphate Levels Endocrinology, May 1, 2008; 149(5): 2391 - 2402. [Abstract] [Full Text] [PDF]

				A. E. Gonzalez-Iglesias, T. Murano, S. Li, M. Tomic, and S. S. Stojilkovic Dopamine Inhibits Basal Prolactin Release in Pituitary Lactotrophs through Pertussis Toxin-Sensitive and -Insensitive Signaling Pathways Endocrinology, April 1, 2008; 149(4): 1470 - 1479. [Abstract] [Full Text] [PDF]

				S. Constantin and S. Wray Gonadotropin-Releasing Hormone-1 Neuronal Activity Is Independent of Cyclic Nucleotide-Gated Channels Endocrinology, January 1, 2008; 149(1): 279 - 290. [Abstract] [Full Text] [PDF]

				N. Vardjan, M. Stenovec, J. Jorgacevski, M. Kreft, and R. Zorec Elementary properties of spontaneous fusion of peptidergic vesicles: fusion pore gating J. Physiol., December 15, 2007; 585(3): 655 - 661. [Abstract] [Full Text] [PDF]

				K. Tsaneva-Atanasova, A. Sherman, F. van Goor, and S. S. Stojilkovic Mechanism of Spontaneous and Receptor-Controlled Electrical Activity in Pituitary Somatotrophs: Experiments and Theory J Neurophysiol, July 1, 2007; 98(1): 131 - 144. [Abstract] [Full Text] [PDF]