Hlavní oblasti výzkumu:
1. Struktůra a funkce purinergních P2X receptorů.
2. Purinergní signalizace v hypothalamu.
3. Melatoninové receptory a excitabilita neonatálních gonádotropních
buněk hypofýzy.
Laboratoř se věnuje výzkumu hypofýzy a hypothalamu. Hlavní zájem je
soustředěn na expresi a funkci melatoninových a purinergních P2X
receptorů, které kontrolují intracelulární vápníkovou signalizaci a
sekreci hormonů v gonádotropních buňkách hypofýzy. Elektrofyziologickými
a mikrofluorimetrickými technikami je studován vliv melatoninu na
intracelulární Ca2+ signalizaci stimulovanou GnRH v primární kultuře
neonatálních hypofyzárních buněk. V neuronech suprachiasmatického jádra
(SCN) a supraoptického jádra (SON) v mozkových řezech hypothalamu je
studována exprese a fyziologické vlastnosti receptorů, které by mohly
hrát roli v synaptickém přenosu a synchronizaci SCN neuronů. V
organotypických řezech ze suprachiasmatického jádra je monitorován
cirkadiánní výlev ATP. Výzkum v poslední době je zaměřen na vztah mezi
strukturou a funkcí rekombinantních melatoninových a purinergních P2X
receptorů, které jsou studovány pomocí bodových mutací a po expresi
mutovaných receptorů v HEK293 buňkách.
PUBLIKACE:
(Autoři z laboratoře jsou podtrženi)
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, 2009 (in press)
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 . |