Skip to main content
SpringerLink
Log in

Biphasic increase in cytosolic free calcium induced by bradykinin and histamine in cultured tracheal smooth muscle cells: is the sustained phase artifactual?

  • Original Articles
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The effects of bradykinin (BK) and histamine on intracellular Ca2+ ([Ca2+]i) were studied in fura-2-loaded guinea-pig tracheal smooth muscle cells in culture. BK, at 10 nM, and histamine, at 100 μM, induced a rise in [Ca2+]i which was inhibited by the B2 antagonist Hoe 140 and by the H1 antagonist triprolidine, respectively. This rise in [Ca2+]i is biphasic, consisting of a rapid transient phase followed by a sustained phase. The transient phase, induced by either BK or histamine, was strongly inhibited by thapsigargin, a microsomal Ca2+-ATPase inhibitor, usually used to deplete certain intracellular Ca2+-stores. Ni2+ (4 mM) did not affect the transient phase but abolished the sustained phase when cells were stimulated by BK, further supporting the fact that the transient phase was only dependent on intracellular Ca2+ pools. The sustained phase was partially (for BK) and completely (for histamine) inhibited by 30 μM Mn2+. This effect could be completely reversed by the addition of DTPA, a cell-impermeant chelator of Mn2+, indicating that the Mn2+ exerted its effect extracellularly. The presence of 1 mM probenecid (an inhibitor of a membrane organic anion transporter that extrudes fura-2) drastically inhibited the sustained phase by more than 77010 for BK and 88010 for histamine. Our results suggest that the effects of BK and histamine on airway smooth muscle cells are mediated via bradykinin B2 receptors and histamine H1 receptors, respectively whose activation allows the rapid transient rise in [Ca2+]i from thapsigargin-sensitive intracellular Ca2+ pools. The sustained phase is proposed to be drastically influenced by an acceleration of fura-2 extrusion during the increase of [Ca2+]i via a probenecid-sensitive mechanism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BK:

bradykinin

[Ca2+]i :

cytosolic free calcium

CICR:

Ca2+-induced Ca2+ release

DMEM:

Dulbecco's modified Eagle's medium

DTPA:

diethylenetriaminepentaacetic acid

EGTA:

ethylene glycol-bis(b-aminoethylether) N,N,N′,N′-tetraacetic acid

FCS:

fetal calf serum

HEPES:

2-[4-(2-Hydroxyethyl)-1-piperazinyl]-ethansulfonic acid

IP:

inositol phosphates

TG:

thapsigargin

TSMC:

tracheal smooth muscle cells

References

  • Almers W, Neher E (1985) The Ca2+ signal from fura-2 loaded mast cells depends strongly on the method of dye loading. FEBS Lett 192:13–18

    Google Scholar 

  • Amrani Y, Bieth O, Landry Y, Bronner C (1994) Effect of lipopolysaccharide on Bradykinin- and Histamine-induced increase in cytosolic free calcium in cultured guinea-pig tracheal smooth muscle cells. Neuropeptides 26:63

    Google Scholar 

  • Amrani Y, Bronner C (1993) Tumor necrosis factor alpha potentiates the increase in cytosolic free calcium induced by bradykinin in guinea-pig tracheal smooth muscle cells. C R Acad Sci Paris/Life sci 316:1489–1494

    Google Scholar 

  • Amrani Y, Da Silva A, Landry Y (1992) Activation by bradykinin of phospholipase A2 in guinea-pig trachea. Fundam Clin Pharmacol 6:401

    Google Scholar 

  • Arakawa H, Kawikova I, Löfdahl CG, Lotvall J (1992) Bradykinin-induced airway response in guinea-pig: effect of inhibition of cyclooxygenase and thromboxane synthetase. Eur J Pharmacol 229: 131–136

    Google Scholar 

  • Arkhammar P, Nilsson T, Berggren PO (1989) Glucose-stimulated efflux of fura-2 in pancreatic \-cells is prevented by probenecid. Biochem Biophys Res Commun 159:223–228

    Google Scholar 

  • Berridge MJ, Irvine RF (1989) Inositol phosphates and cells signalling. Nature 341:197–205

    Google Scholar 

  • Bibb PC, Cochrane DE, Morel-Laurens N (1986) Loss of quin-2 accompanies degranulation of mast cells. FEBS Lett 209:169–174

    Google Scholar 

  • Bramley AM, Samhoun M, Piper PJ (1990) The role of epithelium in modulating the responses of guinea-pig trachea induced by bradykinin. Br J Pharmacol 99:762–766

    Google Scholar 

  • Bronner C, Landry Y (1991) The use of the potential sensitive fluorescent probe bisoxonol in mast cells. Biochim Biophys Acta 1070: 321–331

    Google Scholar 

  • Bronner C, Landry Y, Fontenau P, Kuhry JG (1986). A fluorescent hydrophobic probe used for monitoring the kinetics of exocytotic phenomena. Biochemistry 25:2149–2154

    Google Scholar 

  • Buchan KW, Martin W (1991) Bradykinin induced elevations of cytosolic calcium through mobilisation of intracellular and extracellular pools in bovine aortic endothelial cells. Br J Pharmacol 102:35–40

    Google Scholar 

  • Daykin K, Widdop S, Hall IP (1993) Control of histamine induced inositol phospholipid hydrolysis in cultured human tracheal smooth muscle cells. Eur J Pharmacol 246:135–140

    Google Scholar 

  • Di Virglio F, Steinberg TH, Swanson JA, Silverstein SC (1988) Fura-2 secretion and sequestration in macrophages. A blocker of organic anion transport reveals that these processes occur via a membrane transport system for organic anions. J Immunol 140:915–920

    Google Scholar 

  • Dolor RJ, Hurwitz LM, Mirza Z, Strauss HC, Whorton AR (1992) Regulation of extracellular Ca 2+-entry in endothelial cells. Role of intracellular calcium pool. Am J Physiol 262:C171-C181

    Google Scholar 

  • Farmer SG, Ensor JE, Burch RM (1991) Evidence that cultured airway smooth muscle cells contain bradykinin B2 and B3 receptors. Am J Respir Cell Mol Biol 4:273–277

    Google Scholar 

  • Fasolato C, Pandiela A, Meldolesi J, Pozzan T (1988) Generation of inositol phosphates, cytosolic Ca2+, and ionic fluxes in PC12 cells treated with bradykinin. J Biol Chem 263:17350–17359

    Google Scholar 

  • Fuller RW Dixon CMS, Cuss FMC, Barnes PJ (1987) Bradykinin induced bronchoconstriction in humans. Am Rev Respir Dis 135:176–180

    Google Scholar 

  • Grynkiewicz G, Poenic M, Tsien YR (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260:3340–3450

    Google Scholar 

  • Ichinose M, Belvisi M, Barnes PJ (1990) Bradykinin-induced bronchoconstriction in guinea-pig in vivo: Role of neural mechanisms. J Pharmacol Exp Ther 253:594–599

    Google Scholar 

  • Iredale PA, Kendall DA, Martin KF, Hill SJ (1990) Agonist-induced stimulation of [Ca2+]i in NIE-115 cells: use of manganese to quench extracellular fura-2. Proc Br Pharmacol Soc P107

  • Irvine RF (1990) Quantal Ca2+ release and the control of Ca2+ entry by inositol phosphate — a possible mechanism. FEBS Lett 263:5–9

    Google Scholar 

  • Kwan CY, Takemura H, Obie JF, Thastrup O, Putney JW Jr (1990) Effects of McCh, thapsigargin, and La 3+ on plasmalemmal and intracellular Ca2+ transport in lacrimal cells. Am J Physiol 258: C1006-C1015

    Google Scholar 

  • Marmy N, Mottas J, Durand J (1993) Signal transduction in smooth muscle cells from human airways. Respirat Physiol 91:295–306

    Google Scholar 

  • Marsh KA, Hill SJ (1992) Bradykinin B2 receptor-mediated phosphoinositide hydrolysis in bovine cultured tracheal smooth muscle cells. Br J Pharmacol 107:443–447

    Google Scholar 

  • Marsh KA, Hill SJ (1993) Characteristics of the bradykinin-induced changes in intracellular calcium ion concentration of single bovine tracheal smooth muscle cells. Br J Pharmacol 110:29–35

    Google Scholar 

  • Marthan R (1992) Mécanismes cellulaires de la contraction du muscle lisse bronchique. Arch Int Physiol Biochim Biophys 100:A27-A40

    Google Scholar 

  • Marthan R, Crevel H, Guénard H, Savineau JP (1992) Responsiveness to histamine in human sensitized airway smooth muscle. Respirat Physiol 90:239–250

    Google Scholar 

  • Merrit JE, Jacob R, Hallam TJ (1989) Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. J Biol Chem 264:1522–1527

    Google Scholar 

  • Mikki I, Kase H, Ishii I (1992a) Differences in activities of thromboxane A2 receptor antagonists in smooth muscle cells. Eur J Pharmacol 227:199–204

    Google Scholar 

  • Mikki I, Nonaka H, Ishii I (1992b) Characterization of thromboxane A2/prostaglandin H2 receptors and histamine H1 receptors in cultured guinea-pig tracheal smooth-muscle cells. Biochim Biophys Acta 1137:107–115

    Google Scholar 

  • Murray RK, Kotlikoff MI (1991) Receptor-activated calcium influx in human airway smooth muscle cells. J Physiol 435:123–144

    Google Scholar 

  • Putney JW (1990) Capacitative calcium-entry revisited. Cell Calcium 11:611–624

    Google Scholar 

  • Pyne S, Pyne NJ (1993) Differential effects of B2 receptor antagonists upon bradykinin-stimulated phospholipase C and D in guinea-pig cultured tracheal smooth muscle. Br J Pharmacol 11:477–481

    Google Scholar 

  • Schilling WP, Elliot SJ (1992) Ca2+ signalling mechanisms of vascular endothelial cells and their role in oxidant-induced endothelial cell dysfunction. Am J Physiol 262:H1617-H1630

    Google Scholar 

  • Steinberg TH, Newmann AS, Swanson JA, Silverstein SC (1987) Macrophages posses probenecid-inhibitable organic anion transporters that remove fluorescent dyes from the cytoplasmic matrix. J Cell Biol 105:2695–2702

    Google Scholar 

  • Takatis DN, Dolce C, Hagel-Bradway, Dziak (1992) Second messenger systems stimulated by bradykinin in osteoclastic cells: evidence for B2-receptors. Bone Mineral 18:1–14

    Google Scholar 

  • Takemura H, Ohshida H, Yokosawa N, Oguma K, Thastrup O (1991) The thapsigargin-sensitive intracellular Ca2+ pool is more important in plasma membrane Ca2+ entry than the IP3-sensitive intracellular pool Ca2+ pool in neuronal cell lines. Biochem Biophys Res Commun 180:1518–1526

    Google Scholar 

  • Thastrup O (1990) Role of Ca2+-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2+-ATPase inhibitor, thapsigargin. Agent Action 29:8–15

    Google Scholar 

  • Thastrup O, Dawson AP, Scharff O, Foder B, Cullen PJ, Drobak BJ, Bjerrum PJ, Christensen SB, Hanley MR (1992) Thapsigargin, a novel molecular probe for studying intracellular calcium release and storage. Agent Action 27:17–23

    Google Scholar 

  • Trifilieff A, Amrani Y, Landry Y, Gies JP (1993) Comparative action of new highly potent bradykinin receptor antagonists in the guineapig trachea. Eur J Pharmacol 239:227–229

    Google Scholar 

  • Trifilieff A, Da Silva A, Landry Y, Gies JP (1992) Effect of Hoe 140, a new B2 non-competitive antagonist, on guinea-pig tracheal bradykinin receptors. J Pharmacol Exp Ther 263:1377–1383

    Google Scholar 

  • Tsunoda Y (1993) Receptor-operated Ca2+ signaling and crosstalk in stimulus secretion coupling. Biochim Biophys Acta 1154:105–156

    Google Scholar 

  • Twort C, Van Breemen C (1988) Human airway smooth muscle in culture. Tiss Cell 20:339–344

    Google Scholar 

  • Twort CHC, Van Breemen C (1989) Human airway smooth muscle in cell culture: control of the intracellular calcium store. Pulm Pharmacol 2:45–53

    Google Scholar 

  • Van Breemen C, Saida K (1989) Cellular mechanisms regulating [Ca2+], smooth muscle. Ann Rev Physiol 51:315–329

    Google Scholar 

  • Wirth KJ, Gehring D, Scholkens BA (1993) Effect of Hoe 140 on bradykinin-induced bronchoconstriction in anesthetized guinea-pigs. Am Rev Resp Dis 148:702–706

    Google Scholar 

  • Yang CM, Hsia H-C, Chou S-P, Ong R, Hsieh JT, Luo SF (1994) Bradykinin stimulated phosphoinositide metabolism in cultured canine tracheal smooth muscle cells. Br J Pharmacol 111:21–28

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Neuroimmunopharmacologie, Faculté de Pharmacie, INSERM CJF 91-05, Université Louis Pasteur I, 74 rte du Rhin, B.P. 24, F-67401, Illkirch, France

    Yassine Amrani, Angelo Da Silva, Olivier Kassel & Christian Bronner

Authors
  1. Yassine Amrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angelo Da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olivier Kassel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Bronner
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Correspondence to: C. Bronner

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amrani, Y., Silva, A.D., Kassel, O. et al. Biphasic increase in cytosolic free calcium induced by bradykinin and histamine in cultured tracheal smooth muscle cells: is the sustained phase artifactual?. Naunyn-Schmiedeberg's Arch Pharmacol 350, 662–669 (1994). https://doi.org/10.1007/BF00169372

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00169372

Key words

Search

Navigation