Main Topics:
1. Structure and function of purinergic P2X receptors.
2. Purinergic signaling in pituitary and hypothalamus.
3. Melatonin receptors and excitability of pituitary cells.


Research:
Laboratory is focused on the research of pituitary and hypothalamus. The main interest is on functional expression of purinergic P2X receptors and melatonin receptors that control intracellular calcium signaling, excitability and secretion of hormones from pituitary gland. Using perforated patch clamp recording, microfluorimetric techniques and radioimmunoassay, the effect of melatonin on GnRH-stimulated electrical activity, Ca2+ oscillations is studied in primary culture of neonatal pituitary cells. In neurons of suprachiasmatic nuclei (SCN) and supraoptic nuclei (SON) in hypothalamic rat brain slices, modulation of synaptic transmission and physiological and pharmacological properties of purinergic P2X receptors are investigated. Recent research is focused on structure and function relationship of ATP-gated ion channels studied using mutagenesis and expression of mutated receptors in transfected HEK293 cells.
 

PUBLICATIONS:
(Authors of the Department are underlined.)

2011
Jindrichova M, Khafizov K, Skorinkin A, Fayuk D, Bart G, Zemkova H, Giniatullin R: Highly conserved tyrosine 37 stabilizes desensitized states and restricts calcium permeability of ATP-gated P2X3 receptor. J Neurochem 119:676-685, 2011. Petrenko N, Khafizov K, Tvrdonova V, Skorinkin A, Giniatullin R: Role of the ectodomain serine 275 in shaping the binding pocket of the ATP-gated P2X3 receptor. Biochemistry 50:8427-8436, 2011.
Vavra V, Bhattacharya A, Zemkova H: Facilitation of glutamate and GABA release by P2X receptor activation in supraoptic neurons from freshly isolated rat brain slices. Neuroscience 188:1-12, 2011.
Zemkova H, Stojilkovic SS, Klein DC: Norepinephrine causes a biphasic change in mammalian pinealocye membrane potential: role of alpha1B-adrenoreceptors, phospholipase C, and Ca2+. Endocrinology 152:3842-3851, 2011.

2010
Stojilkovic SS, He ML, Koshimizu TA, Balik A, Zemkova H: Signaling by purinergic receptors and channels in the pituitary gland. Mol Cell Endocrinol. 314: 184-191, 2010.
Kucka M, Kretschmannova K, Murano T, Wu CP, Zemkova H, Ambudkar SV, Stojilkovic SS: Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance. Mol Pharmacol. 77: 270-279, 2010.
Zemkova H, Kucka M, Li S, Gonzalez-Iglesias AE, Tomic M, Stojilkovic SS: Characterization of purinergic P2X4 receptor channels expressed in anterior pituitary cells. Am J Physiol Endocrinol Metab. 298: E644-651, 2010.
Rokic MB, Tvrdonova V, Vavra V, Jindrichova M, Obsil T, Stojilkovic SS, Zemkova H: Roles of conserved ectodomain cysteines of the rat P2X4 purinoreceptor in agonist binding and channel gating. Physiol Res. 59: 927-935, 2010.

2009
Balík A, Jindrichová M, Bhattacharyya S, Zemková H: GnRH-I and GnRH-II-induced calcium signaling and hormone secretion in neonatal rat gonadotrophs. Phys Res 58 (5), 2009 (in press).
Jindrichova M, Vavra V, Obsil T, Stojilkovic SS, Zemkova H: Functional relevance of aromatic residues in the first transmembrane domain of P2X receptors. J Neurochem. 109: 923-934, 2009.

2008
Jelínková I, Vávra V, Jindrichová M, Obsil T, Zemková HW, Zemková H, Stojilkovic SS: Identification of P2X4 Receptor Transmembrane Residues Contributing to Channel Gating and Interaction with Ivermectin. Pflugers Arch, 456: 939-950, 2008.
Zemkova WH, Bjelobaba I, Tomic M, Zemkova H, Stojilkovic SS: Characterization of Depolarizing GABAA Receptor-Channels in Anterior Pituitary Cells. J Physiol 586: 3097–3111, 2008
Mazna P, Grycova L, Balik A, Zemkova H, Friedlova E, Obsilova V, Obsil T, Teisinger J:The role of proline residues in the structure and function of human MT2 melatonin receptor. J Pineal Res. 45:361-372. 2008 .
Zemková H, Balík A, Jindrichová M, Vávra V: Molecular Structure of Purinergic P2X Receptors and their Expression in the Hypothalamus and Pituitary. Physiol Res. 2008 May 13. Phys Res 57: S23-S38, 2008.
Zemkova H, Balik A, Mazna P: Melatonin Inhibition of Gonadotropin-Releasing Hormone-Induced Calcium Signaling and Hormone Secretion in Neonatal Pituitary Gonadotrophs. Chapter 5, pp.59-82. In: Haldar C, Singaravel M, Pandi-Perumal SR, Cardinali DP eds. Experimental Endocrinology and Reproductive Biology. Georgetown, TX, ISBN 978-1-57808-518-7; February 2008; 335 pages, © 2008 LANDES BIOSCIENCE

2007
Zemkova H, Yan Z, Liang Z, Jelinkova I, Tomic M., Stojilkovic SS (2007) Role of Aromatic and Charged Ectodomain Residues in the P2X4 Receptor Functions. J Neurochem 102:1139-1150, 2007.

2006
Zemkova H, Balik A, Jiang Y, Kretschmannova K, Stojilkovic SS (2006) Roles of purinergic P2X receptors as pacemaking channels and modulators of calcium-mobilizing pathway in pituitary gonadotrophs. Mol Endocrinol 20:1423-1436.
Gonzalez-Iglesias AE, Jiang Y, Tomic M, Kretschmannova K, Andric SA, Zemkova H, Stojilkovic SS (2006) Dependence of electrical activity and calcium influx-controlled prolactin release on adenylyl cyclase signaling pathway in pituitary lactotrophs. Mol Endocrinol 20:2231-2246.
Jelinkova I, Yan Z, Liang Z, Moonat S, Teisinger J, Stojilkovic SS, Zemkova H (2006) Identification of P2X(4) receptor-specific residues contributing to the ivermectin effects on channel deactivation. Biochem Biophys Res Commun 349:619-625.
Kretschmannova K, Gonzalez-Iglesias AE, Tomic M, Stojilkovic SS (2006) Dependence of hyperpolarisation-activated cyclic nucleotide-gated channel activity on basal cyclic adenosine monophosphate production in spontaneously firing GH3 cells. J Neuroendocrinol 18:484-493.
Koshimizu TA, Kretschmannova K, He ML, Ueno S, Tanoue A, Yanagihara N, Stojilkovic SS, Tsujimoto G (2006) Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors. Mol Pharmacol 69:1588-1598.
Gonzalez-Iglesias AE, Kretschmannova K, Tomic M, Stojilkovic SS (2006) ZD7288 inhibits exocytosis in an HCN-independent manner and downstream of voltage-gated calcium influx in pituitary lactotrophs. Biochem Biophys Res Commun 346:845-850.

2005
Stojilkovic SS, Tomic M, He ML, Yan Z, Koshimizu T, Zemkova H (2005) Molecular Dissection of Purinergic P2X Receptor-Channels. Ann N Y Acad Sci 1048, 116-130.
Kretschmannova K, Svobodova I, Balik A, Mazna P & Zemkova H (2005) Circadian Rhythmicity in AVP Secretion and GABAergic Synaptic Transmission in the Rat Suprachiasmatic Nucleus. Ann N Y Acad Sci 1048, 103-15.
Mazna P, Berka K, Jelinkova I, Balik A, Svoboda P, Obsilova V, Obsil T, Teisinger J (2005) Ligand binding to the human MT2 melatonin receptor: the role of residues in transmembrane domains 3, 6, and 7. Biochem Biophys Res Commun 332, 726-34.
Stojilkovic SS, Zemkova H & Van Goor F (2005) Biophysical basis of pituitary cell type-specific Ca2+ signaling-secretion coupling. Trends Endocrinol Metab 16, 152-9.
Zemková H, Balík A, Stojilkovic SS (2005) Expression and Signal Transduction Pathways of Melatonin Receptors in Pituitary. Chapter 8, In: Pandi-Perumal SR, Cardinali DP eds. Melatonin: Biological Basis of its Function in Health and Disease. Georgetowen, TX Landis Bioscience, 1-19, http://www.eurekah.com

2004
Balik A, Kretschmannova K, Mazna P, Svobodova I & Zemkova H (2004) Melatonin action in neonatal gonadotrophs. Physiol Res 53 Suppl 1, S153-66.
Kretschmannova K & Zemkova H (2004) Characterization of neuromuscular transmission in mice with progressive motoneuronopathy. Physiol Res 53, 541-8.
Mazna P, Obsilova V, Jelinkova I, Balik A, Berka K, Sovova Z, Ettrich R, Svoboda P, Obsil T & Teisinger J (2004) Molecular modeling of human MT2 melatonin receptor: the role of Val204, Leu272 and Tyr298 in ligand binding. J Neurochem 91, 836-42.
Wise PM, Radil T & Wysocki CJ (2004) Temporal integration in nasal lateralization and nasal detection of carbon dioxide. Chem Senses 29, 137-42.
Zemkova H, Balik A, Kretschmannova K, Mazna P & Stojilkovic SS (2004) Recovery of Ins(1,4,5)-trisphosphate-dependent calcium signaling in neonatal gonadotrophs. Cell Calcium 36, 89-97.
Zemkova H, He ML, Koshimizu TA & Stojilkovic SS (2004) Identification of ectodomain regions contributing to gating, deactivation, and resensitization of purinergic P2X receptors. J Neurosci 24, 6968-78.

2003
He ML, Zemkova H, Koshimizu TA, Tomic M & Stojilkovic SS (2003) Intracellular calcium measurements as a method in studies on activity of purinergic P2X receptor channels. Am J Physiol Cell Physiol 285, C467-79.
He ML, Zemkova H & Stojilkovic SS (2003) Dependence of purinergic P2X receptor activity on ectodomain structure. J Biol Chem 278, 10182-8.
Kretschmannova K, Svobodova I & Zemkova H (2003) Day-night variations in zinc sensitivity of GABAA receptor-channels in rat suprachiasmatic nucleus. Brain Res Mol Brain Res 120, 46-51.
Svobodova I, Vanecek J & Zemkova H (2003) The bidirectional phase-shifting effects of melatonin on the arginine vasopressin secretion rhythm in rat suprachiasmatic nuclei in vitro. Brain Res Mol Brain Res 116, 80-5.
Wise PM, Wysocki CJ & Radil T (2003) Time-intensity ratings of nasal irritation from carbon dioxide. Chem Senses 28, 751-60.
Wysocki CJ, Cowart BJ & Radil T (2003) Nasal trigeminal chemosensitivity across the adult life span. Percept Psychophys 65, 115-22 .