Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Jul 15;486(Pt 2):273–282. doi: 10.1113/jphysiol.1995.sp020810

Histamine and ATP mobilize calcium by activation of H1 and P2u receptors in human lens epithelial cells.

R A Riach 1, G Duncan 1, M R Williams 1, S F Webb 1
PMCID: PMC1156519  PMID: 7473195

Abstract

1. Cytoplasmic calcium concentration ([Ca2+]1) of single superfused tissue-cultured human lens epithelial cells (HLEC) was monitored using the fluorescent dye fura-2; the resting values were low and stable for several hours ([Ca2+]i = 96 +/- 20 nM; mean +/- S.D., n = 16). 2. Continuous superfusion with either ATP or histamine (0.1-10 microM) produced regular oscillations in [Ca2+]i that could be maintained for a short time in the absence of external calcium. 3. Short (30 s) pulses of histamine (0.1-100 microM) induced a transient rise in [Ca2+]i, the time course of which was insensitive to the removal of external calcium. The rate of rise and the amplitude of the response were very sensitive to agonist concentration, whereas the rate of recovery was relatively constant. 4. The responses to long pulses of histamine (> 100 s) consisted of an initial transient followed by a maintained [Ca2+]i which returned to baseline on removal of external calcium. 5. The kinetics of the responses to short and long pulses of ATP (0.1-100 microM) were very similar to those of histamine and showed a similar sensitivity to the presence or absence of external calcium. 6. The histamine responses were abolished by triprolidine (1 microM), but unaffected by ranitidine (1 microM), indicating that an Hi receptor subtype is activated by histamine. 7. The ATP responses were reversibly inhibited by suramin and the potency sequence for a range of agonists was ATP = UTP = ATP gamma S > ADP = GTP >> AMP = adenosine, indicating that activation of a P2u receptor subtype was responsible for the increase in [Ca2+]i. 8. Both histamine and ATP responses were abolished by thapsigargin (100 nM), confirming that calcium release from intracellular stores was responsible for the initial peak of the response. Application of either agonist during the plateau phase of the thapsigargin response often led to a marked, but reversible, decline in [Ca2+]i, indicating the presence of a further, normally hidden, calcium regulatory factor associated with the presence of the agonist. 9. Maximal concentrations of either histamine or ATP totally emptied the calcium store as a subsequent application of the other agonist (or thapsigargin), in the absence of external calcium, failed to induce a further increase in the calcium signal.

Full text

PDF
273

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
  2. Bers D. M. A simple method for the accurate determination of free [Ca] in Ca-EGTA solutions. Am J Physiol. 1982 May;242(5):C404–C408. doi: 10.1152/ajpcell.1982.242.5.C404. [DOI] [PubMed] [Google Scholar]
  3. Bootman M. D., Berridge M. J., Taylor C. W. All-or-nothing Ca2+ mobilization from the intracellular stores of single histamine-stimulated HeLa cells. J Physiol. 1992 May;450:163–178. doi: 10.1113/jphysiol.1992.sp019121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Crawford K. M., MacCallum D. K., Ernst S. A. Agonist-induced Ca2+ mobilization in cultured bovine and human corneal endothelial cells. Curr Eye Res. 1993 Apr;12(4):303–311. doi: 10.3109/02713689308999454. [DOI] [PubMed] [Google Scholar]
  5. Crawford K. M., MacCallum D. K., Ernst S. A. Histamine H1 receptor-mediated Ca2+ signaling in cultured bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 1992 Oct;33(11):3041–3049. [PubMed] [Google Scholar]
  6. Crook R. B., Polansky J. R. Neurotransmitters and neuropeptides stimulate inositol phosphates and intracellular calcium in cultured human nonpigmented ciliary epithelium. Invest Ophthalmol Vis Sci. 1992 Apr;33(5):1706–1716. [PubMed] [Google Scholar]
  7. Den Hertog A., Hoiting B., Molleman A., Van den Akker J., Duin M., Nelemans A. Calcium release from separate receptor-specific intracellular stores induced by histamine and ATP in a hamster cell line. J Physiol. 1992 Aug;454:591–607. doi: 10.1113/jphysiol.1992.sp019281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Duncan G., Webb S. F., Dawson A. P., Bootman M. D., Elliott A. J. Calcium regulation in tissue-cultured human and bovine lens epithelial cells. Invest Ophthalmol Vis Sci. 1993 Sep;34(10):2835–2842. [PubMed] [Google Scholar]
  9. Dunn P. M., Blakeley A. G. Suramin: a reversible P2-purinoceptor antagonist in the mouse vas deferens. Br J Pharmacol. 1988 Feb;93(2):243–245. doi: 10.1111/j.1476-5381.1988.tb11427.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fraser P. J., Duncan G., Tomlinson J. Effect of a cholinesterase inhibitor on salmonid lens: a possible cause for the increased incidence of cataract in salmon Salmo salar (L.). Exp Eye Res. 1989 Aug;49(2):293–298. doi: 10.1016/0014-4835(89)90099-7. [DOI] [PubMed] [Google Scholar]
  11. GOLDMANN H. SENILE CHANGES OF THE LENS AND THE VITREOUS. THE ARTHUR J. BEDELL LECTURE. Am J Ophthalmol. 1964 Jan;57:1–13. doi: 10.1016/0002-9394(64)92026-4. [DOI] [PubMed] [Google Scholar]
  12. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  13. Ireland M. E., Shanbom S. Lens beta-adrenergic receptors. Functional coupling to adenylate cyclase and photoaffinity labeling. Invest Ophthalmol Vis Sci. 1991 Mar;32(3):541–548. [PubMed] [Google Scholar]
  14. Kahn H. A., Leibowitz H. M., Ganley J. P., Kini M. M., Colton T., Nickerson R. S., Dawber T. R. The Framingham Eye Study. I. Outline and major prevalence findings. Am J Epidemiol. 1977 Jul;106(1):17–32. doi: 10.1093/oxfordjournals.aje.a112428. [DOI] [PubMed] [Google Scholar]
  15. Kalthof B., Bechem M., Flocke K., Pott L., Schramm M. Kinetics of ATP-induced Ca2+ transients in cultured pig aortic smooth muscle cells depend on ATP concentration and stored Ca2+. J Physiol. 1993 Jul;466:245–262. [PMC free article] [PubMed] [Google Scholar]
  16. Lee C. H., Reisine T. D., Wax M. B. Alterations of intracellular calcium in human non-pigmented ciliary epithelial cells of the eye. Exp Eye Res. 1989 Jun;48(6):733–743. doi: 10.1016/0014-4835(89)90060-2. [DOI] [PubMed] [Google Scholar]
  17. Marcantonio J. M., Duncan G., Rink H. Calcium-induced opacification and loss of protein in the organ-cultured bovine lens. Exp Eye Res. 1986 Jun;42(6):617–630. doi: 10.1016/0014-4835(86)90051-5. [DOI] [PubMed] [Google Scholar]
  18. Meyer T., Stryer L. Calcium spiking. Annu Rev Biophys Biophys Chem. 1991;20:153–174. doi: 10.1146/annurev.bb.20.060191.001101. [DOI] [PubMed] [Google Scholar]
  19. O'Connor S. E., Dainty I. A., Leff P. Further subclassification of ATP receptors based on agonist studies. Trends Pharmacol Sci. 1991 Apr;12(4):137–141. doi: 10.1016/0165-6147(91)90530-6. [DOI] [PubMed] [Google Scholar]
  20. Osborne N. N. Agonist-induced stimulation of cAMP in the lens: presence of functional beta-receptors. Exp Eye Res. 1991 Jan;52(1):105–106. doi: 10.1016/0014-4835(91)90134-z. [DOI] [PubMed] [Google Scholar]
  21. Parr C. E., Sullivan D. M., Paradiso A. M., Lazarowski E. R., Burch L. H., Olsen J. C., Erb L., Weisman G. A., Boucher R. C., Turner J. T. Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3275–3279. doi: 10.1073/pnas.91.8.3275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Philipson B., Kaufman P. L., Fagerholm P., Axelsson U., Bárány E. H. Echothiophate cataracts in monkeys. Electron microscopy and microradiography. Arch Ophthalmol. 1979 Feb;97(2):340–346. doi: 10.1001/archopht.1979.01020010186023. [DOI] [PubMed] [Google Scholar]
  23. Putney J. W., Jr, Bird G. S. The inositol phosphate-calcium signaling system in nonexcitable cells. Endocr Rev. 1993 Oct;14(5):610–631. doi: 10.1210/edrv-14-5-610. [DOI] [PubMed] [Google Scholar]
  24. Rapaport E., Fontaine J. Anticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP pools. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1662–1666. doi: 10.1073/pnas.86.5.1662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Secchi A. G. Cataracts in Uveitis. Trans Ophthalmol Soc U K. 1982;102(Pt 3):390–394. [PubMed] [Google Scholar]
  26. Shaffer R. N., Hetherington J., Jr Anticholinesterase drugs and cataracts. Am J Ophthalmol. 1966 Oct;62(4):613–618. doi: 10.1016/0002-9394(66)92181-7. [DOI] [PubMed] [Google Scholar]
  27. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Unger W. G., Butler J. M. Neuropeptides in the uveal tract. Eye (Lond) 1988;2 (Suppl):S202–S212. doi: 10.1038/eye.1988.144. [DOI] [PubMed] [Google Scholar]
  29. Vivekanandan S., Lou M. F. Evidence for the presence of phosphoinositide cycle and its involvement in cellular signal transduction in the rabbit lens. Curr Eye Res. 1989 Jan;8(1):101–111. doi: 10.3109/02713688909013899. [DOI] [PubMed] [Google Scholar]
  30. Williams M. R., Duncan G., Riach R. A., Webb S. F. Acetylcholine receptors are coupled to mobilization of intracellular calcium cultured human lens cells. Exp Eye Res. 1993 Sep;57(3):381–384. doi: 10.1006/exer.1993.1138. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES