Endocrinology, Vol 136, 3925-3935, Copyright © 1995 by Endocrine Society

ARTICLES

Corticotropin-releasing hormone stimulation of Ca2+ entry in corticotropes is partially dependent on protein kinase A

YA Kuryshev, GV Childs and AK Ritchie
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641, USA.

The modulation of membrane excitability and cytosolic Ca2+ levels by corticotropin-releasing hormone (CRH), (Bu)2cAMP (dBcAMP), and forskolin was examined in enriched populations of cultured rat anterior pituitary corticotropes. CRH (2 or 20 nM), dBcAMP (1 and 5 mM), and forskolin (10 microM) caused a long lasting membrane depolarization accompanied by the onset of cell firing in quiescent cells or by increased firing frequency in spontaneously active cells. All three substances also increased cytosolic Ca2+ levels by increasing the frequency and amplitude of cytosolic Ca2+ transients. These results are consistent with a previous report on human corticotrope tumor cells demonstrating that CRH-induced action potentials lead to enhancement of Ca2+ uptake through voltage-dependent Ca2+ channels. Preincubation with (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), an inhibitor of cAMP-dependent protein kinase A, did not inhibit the CRH- induced depolarization, but attenuated the CRH-induced increase in action potential frequency. H-89 inhibited CRH-induced changes in cytosolic Ca2+ by 69% in spontaneously active cells and by 83% in quiescent cells. In contrast, H-89 completely abolished the effects of dBcAMP and forskolin on membrane potential and cytosolic Ca2+ levels. It is concluded that activation of protein kinase A mediates all of the response to dBcAMP and forskolin, but only a portion of the response to CRH. The portion of the response to CRH that is resistant to H-89 is mediated by a cAMP-independent mechanism.

This article has been cited by other articles:

				E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology Endocr. Rev., May 1, 2006; 27(3): 260 - 286. [Abstract] [Full Text] [PDF]

				A. K. Lee and A. Tse Dominant Role of Mitochondria in Calcium Homeostasis of Single Rat Pituitary Corticotropes Endocrinology, November 1, 2005; 146(11): 4985 - 4993. [Abstract] [Full Text] [PDF]

				S. Seino and T. Shibasaki PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis Physiol Rev, October 1, 2005; 85(4): 1303 - 1342. [Abstract] [Full Text] [PDF]

				V. Mynard, O. Latchoumanin, L. Guignat, J. Devin-Leclerc, X. Bertagna, B. Barre, J. Fagart, O. Coqueret, and M. G. Catelli Synergistic Signaling by Corticotropin-Releasing Hormone and Leukemia Inhibitory Factor Bridged by Phosphorylated 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein at the Nur Response Element (NurRE)-Signal Transducers and Activators of Transcription (STAT) Element of the Proopiomelanocortin Promoter Mol. Endocrinol., December 1, 2004; 18(12): 2997 - 3010. [Abstract] [Full Text] [PDF]

				R. T. Hinkle, E. Donnelly, D. B. Cody, S. Samuelsson, J. S. Lange, M. B. Bauer, M. Tarnopolsky, R. J. Sheldon, S. C. Coste, E. Tobar, et al. Activation of the CRF 2 receptor modulates skeletal muscle mass under physiological and pathological conditions Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E889 - E898. [Abstract] [Full Text] [PDF]

				T. S. Kostic, M. Tomic', S. A. Andric, and S. S. Stojilkovic Calcium-independent and cAMP-dependent Modulation of Soluble Guanylyl Cyclase Activity by G Protein-coupled Receptors in Pituitary Cells J. Biol. Chem., May 3, 2002; 277(19): 16412 - 16418. [Abstract] [Full Text] [PDF]

				M. Tomic, T.-a. Koshimizu, D. Yuan, S. A. Andric, D. Zivadinovic, and S. S. Stojilkovic Characterization of a Plasma Membrane Calcium Oscillator in Rat Pituitary Somatotrophs J. Biol. Chem., December 10, 1999; 274(50): 35693 - 35702. [Abstract] [Full Text] [PDF]

				Y. A. Kuryshev, G. M. Brittenham, H. Fujioka, P. Kannan, C.-C. Shieh, S. A. Cohen, and A. M. Brown Decreased Sodium and Increased Transient Outward Potassium Currents in Iron-Loaded Cardiac Myocytes : Implications for the Arrhythmogenesis of Human Siderotic Heart Disease Circulation, August 10, 1999; 100(6): 675 - 683. [Abstract] [Full Text] [PDF]

				D. Engler, E. Redei, and I. Kola The Corticotropin-Release Inhibitory Factor Hypothesis: A Review of the Evidence for the Existence of Inhibitory as Well as Stimulatory Hypophysiotropic Regulation of Adrenocorticotropin Secretion and Biosynthesis Endocr. Rev., August 1, 1999; 20(4): 460 - 500. [Abstract] [Full Text] [PDF]

				C. J. Rossant, R. D. Pinnock, J. Hughes, M. D. Hall, and S. McNulty Corticotropin-Releasing Factor Type 1 and Type 2{alpha} Receptors Regulate Phosphorylation of Calcium/Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activation of p42/p44 Mitogen-Activated Protein Kinase Endocrinology, April 1, 1999; 140(4): 1525 - 1536. [Abstract] [Full Text]

				Y. Aoki, Y. Iwasaki, M. Katahira, Y. Oiso, and H. Saito Regulation of the Rat Proopiomelanocortin Gene Expression in AtT-20 Cells. I: Effects of the Common Secretagogues Endocrinology, May 1, 1997; 138(5): 1923 - 1929. [Abstract] [Full Text] [PDF]

				M. J. Shipston, J. S. Kelly, and F. A. Antoni Glucocorticoids Block Protein Kinase A Inhibition of Calcium-activated Potassium Channels J. Biol. Chem., April 19, 1996; 271(16): 9197 - 9200. [Abstract] [Full Text] [PDF]

				S. A. Andric, T. S. Kostic, M. Tomic', T.-a. Koshimizu, and S. S. Stojilkovic Dependence of Soluble Guanylyl Cyclase Activity on Calcium Signaling in Pituitary Cells J. Biol. Chem., January 5, 2001; 276(1): 844 - 849. [Abstract] [Full Text] [PDF]