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Senior Investigator

Stanko S. Stojilkovic, Ph.D.

Endocrinology and Reproduction Research Branch
Building 49 Room 6A36
49 Convent Drive MSC4510
Bethesda MD 20892-4510
Office: (301) 496-1638

Fax: (301) 594-7031

Dr. Stojilkovic received a Ph.D. in Physiology and Neuroendocrinology from the University of Novi Sad, Serbia, in 1982. He was Assistant Professor of Physiology at the Institute of Biology, University of Novi Sad, before joining NICHD as a Guest Researcher in 1985, where he worked in the laboratory of Dr. Kevin J. Catt. Dr. Stojilkovic became an Investigator in 1993 and Senior Investigator in 1998, both within the Endocrinology and Reproduction Research Branch of NICHD. His laboratory investigates calcium signaling pathways at the cellular and molecular levels, and determines the manner in which hormones and neurotransmitters utilize calcium as an intracellular messenger in neuroendocrine cells.



Over one hundred neurotransmitters and hormones, acting on their respective receptors and receptor-channels, relay their signals by altering intracellular calcium concentration. For the generation of calcium signals, cells depend on the large electrochemical gradient of calcium across the plasma membrane, or across the endoplasmic reticulum membrane. There are several pathways controlling calcium influx, including ligand-gated receptor-channels and voltage-gated calcium channels. Calcium release from endoplasmic reticulum is activated by G protein-coupled and tyrosine kinase receptors, and is mediated through inositol (1,4,5)-trisphosphate)-sensitive receptor-channels. Many excitable cells also express ryanodine-sensitive calcium release channels in their endoplasmic/sarcoplasmic reticulum, and these are coupled to voltage-gated calcium channels by a mechanism termed calcium-induced calcium release.

The main objectives of current investigations in the Section on Cellular Signaling are to clarify the mechanisms that control calcium signaling and to elucidate the role of calcium ions as intracellular messenger in neuroendocrine and endocrine cells. The approach in the laboratory has been to characterize calcium signaling in these cells from biophysical, physiological, and pharmacological points of view. More recently, we have begun to use molecular biological approaches to identify molecules participating in the generation and control of calcium signals, as well as to address the issues of how the calcium signaling function in these cells is related to the structure of individual receptors and channels. Current research includes studies on the receptor- and intracellular messenger-mediated control of voltage-gated calcium influx; the structure and function of purinergic receptor-channels; cyclic nucleotide-controlled membrane excitability and calcium signaling; the role of calcium in controlling plasma membrane and endoplasmic reticulum excitability; the dependence of cyclic nucleotide production on calcium; and the relevance of the pattern of calcium signaling to cell-type specific hormone secretion patterns.

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  • Claudio Coddou, Ph.D.
    Visiting Fellow
    (301) 435-0267

  • Marek Kucka, Ph.D.
    Visiting Fellow
    (301) 594-3147

  • Shuo Li, Ph.D.
    Visiting Fellow
    (301) 496-7783

  • Melanija Tomic, Ph.D.
    Staff Scientist
    (301) 496-8164

  • Zonghe Yan, M.D., Ph.D.
    Postdoctoral Fellow
    (301) 496-7783

  • 1) Coddou C, Yan Z, Obsil T, Huidobro-Toro JP, Stojilkovic SS (2011)
  • Activation and regulation of purinergic P2X receptor channels
  • Pharmacol Rev, 63, 641-683
  • 2) Yan Z, Khadra A, Sherman A, Stojilkovic SS (2011)
  • Calcium-dependent block of P2X7 receptor channel function is allosteric
  • J Gen Physiol, 138, 437-452
  • 3) Kucka M, Kretschmannova K, Murano T, Wu CP, Zemkova H, Ambudkar SV, Stojilkovic SS (2010)
  • Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance
  • Mol Pharmacol, 77, 270-279
  • 4) Yan Z, Khadra A, Li S, Tomic M, Sherman A, Stojilkovic SS (2010)
  • Experimental characterization and mathematical modeling of P2X7 receptor channel gating
  • J Neurosci, 30, 14213-14224
  • 5) Stojilkovic SS, Tabak J, Bertram R (2010)
  • Ion channels and signaling in the pituitary gland
  • Endocr Rev, 31, 845-915
  • 6) Stojilkovic SS (2009)
  • Purinergic regulation of hypothalamopituitary functions
  • Trends Endocrinol Metab, 20, 460-468
  • 7) Constantin S, Caligioni CS, Stojilkovic S, Wray S (2009)
  • Kisspeptin-10 facilitates a plasma membrane-driven calcium oscillator in gonadotropin-releasing hormone-1 neurons
  • Endocrinology, 150, 1400-1412
  • 8) Jindrichova M, Varva V, Obsil T, Stojilkovic SS, Zemkova H (2009)
  • Functional relevance of aromatic residues in the first transmembrane domain of P2X receptors
  • J Neurochem, 109, 923-934
  • 9) Korzeniowski MK, Popovic MA, Szentpetery Z, Varnai P, Stojilkovic SS, Balla T (2009)
  • Dependence of STIM1/Orai1-mediated calcium entry on plasma membrane phosphoinositides
  • J Biol Chem, 284, 21027-21035
  • 10) Coddou C, Codocedo JF, Li S, Lillo JG, Acuna-Castillo C, Bull P, Stojilkovic SS, Huidobro-Toro JP (2009)
  • Reactive oxygen species potentiate the P2X2 receptor activity through intracellular Cys430
  • J Neurosci, 29, 12284-12291
  • 11) Yan Z, Li S, Liang Z, Tomić M, Stojilkovic SS (2008)
  • The P2X7 receptor channel pore dilates under physiological ion conditions
  • J Gen Physiol, 132, 563-573
  • 12) Gonzalez-Iglesias AE, Murano T, Li S, Tomić M, Stojilkovic SS (2008)
  • Dopamine inhibits basal prolactin release in pituitary lactotrophs through pertussis toxin-sensitive and -insensitive signaling pathways
  • Endocrinology, 149, 1470-1479
  • 13) Jelinkova I, Vavra V, Jindrichova M, Obsil T, Zemkova HW, Zemkova H, Stojilkovic SS (2008)
  • Identification of P2X(4) receptor transmembrane residues contributing to channel gating and interaction with ivermectin
  • Pflugers Arch, 456, 9390950
  • 14) Zemkova HW, Bjelobaba I, Tomic M, Zemkova H, Stojilkovic SS (2008)
  • Molecular, pharmacological and functional properties of GABA(A) receptors in anterior pituitary cells
  • J Physiol, 586, 3097-3111
  • 15) Zemkova H, Yan Z, Liang Z, Jelinkova I, Tomic M, Stojilkovic SS (2007)
  • Role of aromatic and charged ectodomain residues in the P2X(4) receptor functions
  • J Neurochem, 102, 1139-11590
  • 16) Hatae N, Aksentijevich N, Zemkova HW, Kretschmannova K, Tomic M, Stojilkovic SS (2007)
  • Cloning and functional identification of novel endothelin receptor type A isoforms in pituitary
  • Mol Endocirnol, 21, 1192-1204
  • 17) Tsaneva-Atanasova K, Sherman A, van Goor F, Stojilkovic SS (2007)
  • Mechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs: experiments and theory
  • J Neurophysiol, 98, 131-144
  • 18) Jiang Y, Stojilkovic SS. (2006)
  • Molecular cloning and characterization of alpha1-soluble guanylyl cyclase gene promoter in rat pituitary cells.
  • J Mol Endocrinol, 37, 503-515
  • 19) 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, 1588-98
  • 20) 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, 1423-36
  • 21) Andric SA, Kostic TS, Stojilkovic SS. (2006)
  • Contribution of multidrug resistance protein MRP5 in control of cyclic guanosine 5'-monophosphate intracellular signaling in anterior pituitary cells.
  • Endocrinology, 147, 3435-45
  • 22) 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, 2231-46
  • 23) Yan Z, Liang Z, Obsil T, Stojilkovic SS. (2006)
  • Participation of the Lys313-Ile333 sequence of the purinergic P2X4 receptor in agonist binding and transduction of signals to the channel gate.
  • J Biol Chem, 281, 32649-59
  • 24) 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
  • 25) Andric SA, Zivadinovic D, Gonzalez-Iglesias AE, Lachowicz A, Tomic M, Stojilkovic SS. (2005)
  • Endothelin-induced, long lasting, and Ca2+ influx-independent blockade of intrinsic secretion in pituitary cells by Gz subunits.
  • J Biol Chem, 280, 26896-903
  • 27) Yan Z, Liang Z, Tomic M, Obsil T, Stojilkovic SS. (2005)
  • Molecular determinants of the agonist binding domain of a P2X receptor channel.
  • Mol Pharmacol, 67, 1078-88
  • 28) Kostic T, Andric S, Stojilkovic SS (2004)
  • Receptor-controlled phosphorylation of alpha 1 soluble guanylyl cyclase enhances nitric oxide-dependent cyclic guanosine 5'-monophosphate production in pituitary cells
  • Mol Endocrinol, 18, 458-470
  • 29) 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, 6968-6978
  • 30) He ML, Gonzalez-Iglesias AE, Stojilkovic SS (2003)
  • Role of Nucleotide P2 Receptors in Calcium Signaling and Prolactin Release in Pituitary Lactotrophs
  • J Biol Chem , 278, 46270-46277
  • 31) Basta M, Van Goor F, Luccioli S, Billings EM, Vortmeyer AO, Barany L, Szebeni J, Alving CR, Carroll MC, Berkower I, Stojilkovic SS, Metcalfe DD (2003)
  • F(ab)-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins
  • Nature Med , 9, 431-438
  • 32) He ML, Zemkova H, Stojilkovic SS (2003)
  • Dependence of purinergic P2X receptor activity on ectrodomain structure
  • J Biol Chem, 278, 10182-10188
  • 33) He ML, Koshimizu TA, Tomic M, Stojilkovic SS (2002)
  • Purinergic P2X(2) receptor desensitization depends on coupling between ectodomain and C-terminal domain
  • Mol Pharmacol, 62, 1187-1197
  • 34) Kostic TS, Tomic M, Andric SA, Stojilkovic SS (2002)
  • Calcium-independent and cAMP-dependent modulation of soluble guanylyl cyclase activity by G protein-coupled receptors in pituitary cells
  • J Biol Chem, 277, 16412-16418
  • 35) Tomic M, Van Goor F, He ML, Zivadinovic D, Stojilkovic SS (2002)
  • Ca(2+)-mobilizing endothelin-A receptors inhibit voltage-gated Ca(2+) influx through G(i/o) signaling pathway in pituitary lactotrophs
  • Mol Pharmacol, 61, 1329-1339
  • 36) Koshimizu TA, Ueno S, Tanoue A, Yanagihara N, Stojilkovic SS, Tsujimoto G (2002)
  • Heteromultimerization modulates P2X receptor functions through participating extracellular and C-terminal subdomains
  • J Biol Chem, 277, 46891-46899
  • 37) Van Goor F, D Zivadinovic, AJ Martinez-Fuentes & SS Stojilkovic (2001)
  • Dependence of pituitary hormone secretion on the pattern of spontaneous voltage-gated calcium influx: Cell-type specific action potential secretion coupling
  • J Biol Chem, 276, 33840-33846
  • 38) Stojilkovic SS & T Koshimizu (2001)
  • Signaling by extracellular nucleotides in anterior pituitary cells
  • Trends Endocrinol Metab, 12, 218-225
  • 39) Van Goor F, D Zivadinovic & SS Stojilkovic (2001)
  • Differential expression of ionic channels in rat anterior pituitary cells
  • Mol Endocrinol, 15, 1222-1236
  • 40) Koshimizu T, F Van Goor, M Tomic, AOL Wong, A Tanoue, G Tsujimoto & SS Stojilkovic (2001)
  • Characterization of calcium signaling by purinergic receptor-channels expressed in excitable cells
  • Mol Pharmacol, 58, 936-945
  • 41) Andric SA, TS Kostic, M Tomic, T Koshimizu & SS Stojilkovic (2001)
  • Dependence of soluble gyanlylyl cyclase activity on calcium signaling in pituitary cells
  • J Biol Chem, 276, 844-849
  • 42) Kostic TS, SA Andric & SS Stojilkovic (2001)
  • Spontaneous and receptor-controlled soluble guanylyl cyclase activity in anterior pituitary cells
  • Mol Endocrinol, 15, 1010-1022
  • 43) Van Goor F, Y-X Li & SS Stojilkovic (2001)
  • Paradoxical role of large-conductance calcium-activated K+ (BK) channels in controlling action potential-driven Ca2+ entry in anterior pituitary cells
  • J Neurosci, 21, 5902-5915
  • 44) Koshimizu T, M Tomic, AOL Wong, D Zivadinovic & SS Stojilkovic (2000)
  • Characterization of purinergic receptors and receptor-channels expressed in anterior pituitary cells
  • Endocrinology, 141, 4091-4099
  • 45) Van Goor F, AP LeBeau, LZ Krsmanovic, A Sherman, KJ Catt & SS Stojilkovic (2000)
  • Amlitude-dependent spike-broadening and enhanced Ca2+ signaling in GnRH-secreting neurons
  • J Biophys, 79, 1310-1323
  • 46) Van Goor F, LZ Krsmanovic, KJ Catt & SS Stojilkovic (1999)
  • Control of action potential driven calcium influx in GT1 neurons by the activation status of sodium and calcium channels
  • Mol Endocrinol, 13, 587-603
  • 47) Tomic M, D Zivadinovic, F Van Goor, D Yuan, T Koshimizu & SS Stojilkovic (1999)
  • Expression of Ca2+-mobilzing endothelin-A receptors and their role in the control of Ca2+ influx and growth hormone secretion in pituitary somatotrophs
  • J Neurosci , 19, 7721-7731
  • 48) Katzur AC, T Koshimizu, M Tomic, A Schultze-Mosgau, O Ortmann & SS Stojilkovic (1999)
  • Expression and responsiveness of P2Y2 receptors in human endometrial cancer cell lines
  • J Clin Endocrinol Metab, 84, 4085-4091
  • 49) Tomic M, T Koshimizu, D Yuan, SA Andric, D Zivadinovic & SS Stojilkovic (1999)
  • Characterization of a plasma membrane calcium oscillator in rat pituitary somatotrophs
  • J Biol Chem, 274, 35693-35702
  • 50) Koshimizu T, M Koshimizu & SS Stojilkovic (1999)
  • Contributions of the C-terminal domain to the control of P2X receptor desensitization
  • J Biol Chem , 274, 37651-37657
  • 51) Van Goor F, LZ Krsmanovic, KJ Catt & SS Stojilkovic (1999)
  • Coordinate regulation of gonadotropin-releasing hormone neuronal firing patterns by cytosolic calcium and store depletion
  • Proc Nat Acad Sci USA, 96, 4101-4106
  • 52) Koshimizu T, M Tomic, F Van Goor & SS Stojilkovic (1998)
  • Functional role of alternative splicing in pituitary P2X2 receptor-channel activation and desensitization
  • Mol Endocrinol , 12, 901-913
  • 53) Koshimizu T, M Tomic, M Koshimizu & SS Stojilkovic (1998)
  • Identification of amino acid residues contributing to desensitization of the P2X2 receptor-channel
  • J Biol Chem, 273, 12853-12857
  • 54) Zheng L, LZ Krsmanovic, LA Vergara, KJ Catt & SS Stojilkovic (1997)
  • Dependence of intracellular signaling and neurosecretion on phospholipase D activation in immortalized gonadotropin-releasing hormone neurons
  • Proc Natl Acad Sci USA, 94, 1573-1578
  • 55) Kukuljan M, L Vergara & SS Stojilkovic (1997)
  • Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca2+]i oscillations by calcium entry in pituitary gonadotrophs
  • Biophys J, 72, 698-707
  • 56) Rao K, W-Y Paik, L Zheng, RM Jobin, M Tomic, H Jiang, S Nakanishi & SS Stojilkovic (1997)
  • Wortmannin-sensitive and -insensitive steps in calcium-controlled exocytosis in pituitary gonadotrophs
  • Endocrinology, 138, 1440-1449
  • 57) Vergara L, E Rojas & SS Stojilkovic (1997)
  • A novel calcium-activated apamin-insensitive potassium current in pituitary gonadotrophs
  • Endocrinology , 138, 2658-2664
  • 58) Lachowicz A, F Van Goor, AC Katzur, G Bonhomme, & SS Stojilkovic (1997)
  • Uncoupling of calcium mobilization and entry pathways in endothelin-stimulated rat pituitary lactotrophs
  • J Biol Chem, 272, 28308-28314
  • 59) Stojilkovic SS, Catt KJ (1996)
  • Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells
  • Front Neuroendocrinol, 17, 327-369
  • 60) Tomić M, Jobin RM, Vergara LA, Stojilkovic SS (1996)
  • Expression of purinergic receptor channels and their role in calcium signaling and hormone release in pituitary gonadotrophs. Integration of P2 channels in plasma membrane- and endoplasmic reticulum-derived calcium oscillations
  • J Biol Chem, 271, 21200-21208
  • 61) Stojilkovic SS, Tomić M (1996)
  • GnRH-induced calcium and current oscillations in gonadotrophs
  • Trends Endocrinol Metab, 7, 379-384
  • 62) Stojilkovic SS, Catt KJ (1995)
  • Expression and signal transduction pathways of gonadotropin-releasing hormone receptors
  • Recent Prog Horm Res, 50, 161-205
  • 63) Zheng L, Paik WY, Cesnjaj M, Balla T, Tomić M, Catt KJ, Stojilkovic SS (1995)
  • Effects of the phospholipase-C inhibitor, U73122, on signaling and secretion in pituitary gonadotrophs
  • Endocrinology, 136, 1079-1088
  • 64) Cesnjaj M, Zheng L, Catt KJ, Stojilkovic SS (1995)
  • Dependence of stimulus-transcription coupling on phospholipase D in agonist-stimulated pituitary cells
  • Mol Biol Cell, 6, 1037-1047
  • 65) Stojilkovic SS, Catt KJ (1995)
  • Novel aspects of GnRH-induced intracellular signaling and secretion in pituitary gonadotrophs
  • J Neuroendocrinol, 7, 739-757
  • 66) Tomić M, Dufau ML, Catt KJ, Stojilkovic SS (1995)
  • Calcium signaling in single rat Leydig cells
  • Endocrinology, 136, 3422-3429
  • 67) Stojilkovic SS, Krsmanovic LZ, Spergel DJ, Catt KJ (1994)
  • Gonadotropin-releasing hormone neurons: intrinsic pulsatility and receptor-mediated regulation
  • Trends Endocrinol Metab, 5, 201-209
  • 68) Cesnjaj M, Catt KJ, Stojilkovic SS (1994)
  • Coordinate actions of calcium and protein kinase-C in the expression of primary response genes in pituitary gonadotrophs
  • Endocrinology, 135, 692-701
  • 69) Kukuljan M, Rojas E, Catt KJ, Stojilkovic SS (1994)
  • Membrane potential regulates inositol 1,4,5-trisphosphate-controlled cytoplasmic Ca2+ oscillations in pituitary gonadotrophs
  • J Biol Chem, 269, 4860-4865
  • 70) Stojilkovic SS, Tomic M, Kukuljan M, Catt KJ (1994)
  • Control of calcium spiking frequency in pituitary gonadotrophs by a single-pool cytoplasmic oscillator
  • Mol Pharmacol, 45, 1013-1021
  • 71) Stojilkovic SS, Reinhart J, Catt KJ (1994)
  • Gonadotropin-releasing hormone receptors: structure and signal transduction pathways
  • Endocr Rev, 15, 462-499
  • 72) Tomić M, Cesnajaj M, Catt KJ, Stojilkovic SS (1994)
  • Developmental and physiological aspects of Ca2+ signaling in agonist-stimulated pituitary gonadotrophs
  • Endocrinology, 135, 1762-1771
  • 73) Cesnjaj M, Krsmanovic LZ, Catt KJ, Stojilkovic SS (1993)
  • Autocrine induction of c-fos expression in GT1 neuronal cells by gonadotropin-releasing hormone
  • Endocrinology, 133, 3042-3045
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