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Pertussis toxin and N-ethylmaleimide inhibit histamine- but not calcium ionophore-induced endothelium-dependent relaxation

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Summary

Endothelium-dependent relaxation of the guinea pig pulmonary artery induced by histamine was inhibited by preincubation of the tissue with 10 μM N-ethylmaleimide (NEM) for 10 min, whereas the endothelium-dependent relaxation induced by the calcium ionophore A 23187 was not affected by NEM. Pretreatment of the preparations with 0.2–1 μg/ml pertussis toxin for 120 min inhibited concentration-dependently the histamine-induced relaxation. In contrast, endothelium-dependent relaxation in response to the calcium ionophore A 23187 was not affected by pertussis toxin. Since NEM and pertussis toxin are thought to interfere with membrane located GTP binding proteins, it is suggested that such a coupling protein is involved in the signal transduction of the histamine receptor leading to endothelium-dependent relaxation.

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References

  • Asano T, Ogasawara N (1986) Uncoupling of γ-aminobutyric acid B receptors from GTP-binding proteins by N-ethylmaleimide: Effects of N-ethylmaleimide on purified GTP-binding proteins. Mol Pharmacol 29:244–249

    Google Scholar 

  • Babcock DF, First NL, Lardy HA (1976) Action of ionophore A 23187 at the cellular level. Separation of effects at the plasma and mitochondrial membranes. J Biol Chem 251:3881–3886

    Google Scholar 

  • Brass LF, Laposata M, Banga HS, Rittenhouse SE (1986) Regulation of the phosphoinositide hydrolysis pathway in thrombin stimulated platelets by a pertussis toxin-sensitive guanine nucleotide-binding protein. J Biol Chem 261:16838–16847

    Google Scholar 

  • Clark MA, Conway TM, Bennett CF, Crooke ST, Stadel JM (1986) Islet-activating protein inhibits leukotriene D4- and leukotriene C4- but not bradykinin- or calcium ionophore-induced prostacyclin synthesis in bovine endothelial cells. Proc Natl Acad Sci USA 83:7320–7324

    Google Scholar 

  • Cockcroft S, Gomperts BD (1985) Role of guanine nucleotide binding protein in the activation of polyphosphoinoside phosphodiesterase. Nature 314:534–536

    Google Scholar 

  • De Nucci G, Gryglewski RJ, Warner TD, Vane JR (1988) Receptor mediated release of endothelium-derived relaxing factor and prostacyclin from bovine endothelial cells is coupled. Proc Natl Acad Sci USA 85:2334–2338

    Google Scholar 

  • Fain JN, Wallace MA, Wojcikiewicz RJH (1988) Evidence for involvement of guanine nucleotide-binding regulatory proteins in the activation of phospholipases by hormones. FASEB J 2:2569–2574

    Google Scholar 

  • Furchgott RF (1984) The role of endothelium in the responses of vascular smooth muscle to drugs. Ann Rev Pharmacol Toxicol 24:175–197

    Google Scholar 

  • Gilman AG (1986) Receptor-regulated G proteins. Trends Neurosci 9:460–463

    Google Scholar 

  • Gruetter CA, Lemke SM (1986) Effects of sulfhydryl reagents on nitroglycerin-induced relaxation of bovine coronary artery. Can J Physiol Pharmacol 64:1395–1401

    Google Scholar 

  • Harden TK, Scheer AG, Smith Mc HM (1982) Differential modification of the interaction of cardiac muscarinic cholinergic and beta adrenergic receptors with a guanosine nucleotide binding component(s). Mol Pharmacol 21:570–580

    Google Scholar 

  • Jakobs KH, Lasch P, Minuth M, Aktories K, Schultz G (1982) Uncoupling of a-adrenoceptor-mediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem 257:2829–2833

    Google Scholar 

  • Jakobs KH, Minuth M, Bauer S, Grandt R, Greiner C, Zubin P (1986) Dual regulation of adenylate cyclase. A signal transduction mechanism of membrane receptors. Basic Res Cardiol 81:1–9

    Google Scholar 

  • Joseph SK (1985) Receptor-stimulated phosphoinositide metabolism: a role for GTP-binding proteins? Trends Biochem Sci 10:297–298

    Google Scholar 

  • Kanaide H, Matsumoto T, Nakamura M (1986) Inhibition of calcium transients in cultured vascular smooth muscle cells by pertussis toxin. Biochem Biophys Res Commun 140:195–203

    Google Scholar 

  • Lambert TL, Kent RS, Whorton AR (1986) Bradykinin stimulation of inositol polyphosphate production in porcine aortic endothelial cells. J Biol Chem 261:15288–15293

    Google Scholar 

  • Lo WWY, Fan T-PD (1987) Histamine stimulates inositol phosphate accumulation via the H1-receptor in cultured human endothelial cells. Biochem Biophys Res Commun 148:47–53

    Google Scholar 

  • Lo WLY, Hughes J (1987) Pertussis toxin distinguishes between muscarinic receptor-mediated inhibition of adenylate cyclase and stimulation of phosphoinoside hydrolysis in Flow 9000 cells. Febs Lett 220:155–158

    Google Scholar 

  • Murayama T, Ui M (1985) Receptor-mediated inhibition of adenylate cyclase and stimulation of arachidonic acid release in 3T3 fibroblasts. Selective susceptibility to islet-activating protein, pertussis toxin. J Biol Chem 260:7226–7233

    Google Scholar 

  • Nakamura T, Ui M (1985) Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. J Biol Chem 260:3584–3593

    Google Scholar 

  • Nakashima S, Hattori H, Shirato L, Takenaka A, Nozawa Y (1987) Differential sensitivity of arachidonic acid release and 1,2-diacylglycerol formation to pertussis toxin, GDPβS and NaF in saponin-permeabilized human platelets: possible evidence for distinct GTP-binding proteins involving phospholipase C and A2 activation. Biochem Biophys Res Commun 148:971–978

    Google Scholar 

  • Okajima F, Ui M (1984) ADP-ribosylation of the specific membrane protein by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. J Biol Chem 259:13863–13871

    Google Scholar 

  • Osswald H, Sander S, Poeschla E, Forrest JN (1985) Adenosine-receptors in the salt gland of squalus acanthias. In: Andersson KE, Persson CGA (eds) Anti-asthma xanthines and adenosine. Excerpta Medica, Amsterdam, pp 435–439

    Google Scholar 

  • Pfeilschifter J, Bauer C (1986) Pertussis toxin abolishes angiotensin II-induced phosphoinositide hydrolysis and prostaglandin synthesis in rat renal mesangial cells. Biochem J 236:289–294

    Google Scholar 

  • Quennedey M-C, Bockaert J, Rouoft B (1984) Direct and indirect effects of sulfhydryl blocking agents on agonists and antagonists binding to central α1 and α2 adrenoceptors. Biochem Pharmacol 33:3923–3928

    Google Scholar 

  • Reed PW, Lardy HA (1972) Antibiotic A 23187 as a probe for the study of calcium and magnesium function in biological systems. In: Mehlman MA, Hanson RW (eds) The role of membranes in metabolic regulation. Academic Press, New York, pp 111–131

    Google Scholar 

  • Satoh H, Inui J (1984) Endothelial cell-dependent relaxation and contraction induced by histamine in the isolated guinea-pig pulmonary artery. Eur J Pharmacol 97:321–324

    Google Scholar 

  • Schlondorff D, Satriano JA, De Landido S (1986) Different concentrations of pertussis toxin have opposite effects on agonist-induced PGE2 formation in mesangial cells. Biochem Biophys Res Commun 141:39–45

    Google Scholar 

  • Smith CD, Uhing RJ, Snyderman R (1987) Nucleotide regulatory protein-mediated activation of phospholipase C in human polymorphonuclear leucocytes is disrupted by phorbol esters. J Biol Chem 262:6121–6127

    Google Scholar 

  • Ui M (1986) Pertussis toxin as a probe of receptor coupling to inositol lipid metabolism. In: Phosphoinositides and receptor mechanisms. Alan R. Liss, Inc, pp 163–195

  • Ukena D, Poeschla E, Hüttemann E, Schwabe U (1984) Effects of N-ethylmaleimide on adenosine receptors of rat fat cells and human platelets. Naunyn-Schmiedeberg's Arch Pharmacol 327:247–253

    Google Scholar 

  • Wei J-W, Sulakhe PV (1980) Requirement for sulfhydryl groups in the differential effects of magnesium ion and GTP on agonist binding of muscarinic cholinergic receptor sites in rat atrial membrane fraction. Naunyn-Schmiedeberg's Arch Pharmacol 314:51–59

    Google Scholar 

  • Weinheimer G, Osswald H (1986) Inhibition of endothelium-dependent smooth muscle relaxation by calmodulin antagonists. Naunyn-Schmiedeberg's Arch Pharmacol 332:391–397

    Google Scholar 

  • Weinheimer G, Wagner B, Osswald H (1986) Interference of phorbolesters with endothelium-dependent vascular smooth muscle relaxation. Eur J Pharmacol 130:319–322

    Google Scholar 

  • Yeung S-M H, Green RD (1983) Agonist and antagonist affinities for inhibitory adenosine receptors are reciprocally affected by 5′-guanylylimidodiphosphate or N-ethylmaleimide. J Biol Chem 258:2334–2339

    Google Scholar 

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  1. Gödecke Research Institute, Mooswaldallee 1-9, D-7800, Freiburg, Federal Republic of Germany

    G. Weinheimer & H. Osswald

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  1. G. Weinheimer
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  2. H. Osswald
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Weinheimer, G., Osswald, H. Pertussis toxin and N-ethylmaleimide inhibit histamine- but not calcium ionophore-induced endothelium-dependent relaxation. Naunyn-Schmiedeberg's Arch Pharmacol 339, 14–18 (1989). https://doi.org/10.1007/BF00165120

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  • DOI: https://doi.org/10.1007/BF00165120

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