Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 318, Issue 3, pp 181–184 | Cite as

α2-Adrenoceptors inhibit the cholera-toxin-induced intestinal fluid accumulation

  • Toshio Nakaki
  • Teruo Nakadate
  • Satoshi Yamamoto
  • Ryuichi Kato
Article

Summary

The effects of adrenoceptor agonists and antagonists on the cholera-toxin-induced intestinal fluid accumulation and the mucosal levels of cAMP were investigated in vivo. Cholera toxin produced a marked fluid accumulation. Adrenaline inhibited the effect of the toxin in a dose-dependent manner. An α1-adrenoceptor blocking agent yohimbine antagonized the effect of adrenaline. The α1-adrenoceptor blocking agents prazosin and phenoxybenzamine failed to antagonize the effect of adrenaline. A high dose of a β-adrenoceptor blocking agent pindolol did not antagonize the effect of adrenaline. Yohimbine or pindolol alone did not produce any effects on the toxin-induced fluid accumulation. However, prazosin and phenoxybenzamine per se inhibited the toxin-induced fluid accumulation. An α2-selective agonist clonidine was slightly more potent than adrenaline, and was about 100-fold more potent than the α1-selective agonist methoxamine in inhibiting the cholera-toxin-induced intestinal secretion. Clonidine, adrenaline and methoxamine failed to reduce the mucosal levels of cAMP, while these α-adrenoceptor agonists inhibited the toxin-induced fluid accumulation in the same preparations. These results suggest that the stimulation of α2-adrenoceptors inhibit the cholera-toxin-induced intestinal secretion without reducing the whole mucosal levels of cAMP.

Key words

Cholera toxin Intestinal secretion α2-Adrenoceptors 

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References

  1. Aktories K, Shultz G, Jakobs KH (1980) Regulation of adenylate cyclase activity in hamster adipocytes: inhibition by prostaglandins, α-adrenergic agonists and nicotinic acid. Naunyn-Schmiedeberg's Arch Pharmacol 312:167–173Google Scholar
  2. Berthelsen S, Pettinger WA (1977) A functional basis for classification of α-adrenergic receptors. Life Sci 21:595–606Google Scholar
  3. Beubler E, Lembeck F (1980) Inhibition by morphine of prostaglandin E1-stimulated secretion and cyclic adenosine 3′, 5′-monophosphate formation in the rat jejunum in vivo. Br J Pharmacol 68:513–518Google Scholar
  4. Blaschke TF, Melmon KL (1980) Antihypertensive agents and the drug therapy of hypertension. In: Gilman AG, Goodman LS, Gilman A (eds) Goodman's and Gilman's the pharmacological basis of therapeutics. Macmillan Publishing Co., Inc., New York, pp 793–818Google Scholar
  5. Carpenter CCJ, Curlin GT, Greenough WB (1969) Response of canine Thirty-Vella jejunal loops to cholera exotoxin and its modification by ethacrynic acid. Infect Dis 120:332–338Google Scholar
  6. Dubocovich ML, Langer SZ (1980) Pharmacological differentiation of presynaptic inhibitory α-adrenoceptors and opiate receptors in the cat nictitating membrane. Br J Pharmacol 70:383–393Google Scholar
  7. Farack UM, Kautz U, Loeschke K (1981) Loperamide reduces the intestinal secretion but not the mucosal cAMP accumulation induced by choleratoxin. Naunyn-Schmiedeberg's Arch Pharmacol 317:178–179Google Scholar
  8. Field M, McColl I (1973) Ion transport in rabbit ileal mucosa. III. Effects of catecholamines. Am J Physiol 225:852–857Google Scholar
  9. Field M, Sheerin HE, Henderson A, Smith PL (1975) Catecholamine effects on cyclic AMP levels and ion secretion in rabbit ileal mucosa. Am J Physiol 229:86–92Google Scholar
  10. Guerrant RL, Chen LC, Sharp GWG (1972) Intestinal adenylate-cyclase activity in canine cholera: correlation with fluid accumulation. J Infect Dis 125:377–381Google Scholar
  11. Jakobs KH (1978) Synthetic α-adrenergic agonists are potent α-adrenergic blockers in human platelets. Nature 274:819–820Google Scholar
  12. Kimberg DV, Field M, Johnson J, Henderson A, Gershon E (1971) Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. J Clin Invest 50:1218–1230Google Scholar
  13. Lange S, Holmgren J (1978) Protective antitoxic cholera immunity in mice: influence of route and number of immunizations and mode of action of protective antibodies. Acta Pathol Microbiol Scand Sec C 86:145–152Google Scholar
  14. Langer SZ (1974) Presynaptic regulation of catecholamine release. Biochem Pharmacol 23:1793–1980Google Scholar
  15. Langer SZ (1980) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362Google Scholar
  16. Lee MK, Coupar IM (1980) Inhibition of intestinal secretion without reduction of cyclic AMP levels. Eur J Pharmacol 68:501–503Google Scholar
  17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275Google Scholar
  18. Lönnroth I, Holmgren J, Lange S (1977) Chlorpromazine inhibits cholera toxin-induced intestinal hypersecretion. Med Biol 55:126–129Google Scholar
  19. Nakaki T, Nakadate T, Ishii K, Kato R (1981) Postsynaptic alpha-2 adrenergic receptors in isolated rat islets of Langerhans: inhibition of insulin release and cyclic 3′:5′-adenosine monophosphate accumulation. J Pharmacol Exp Ther 216:607–612Google Scholar
  20. Nakaki T, Nakadate T, Yamamoto S, Kato R (1982) Alpha-2-adrenergic inhibition of intestinal secretion induced by prostaglandin E1, vasoactive intestinal peptide and dibutyryl cyclic AMP in rat jejunum. J Pharmacol Exp Ther: in pressGoogle Scholar
  21. Ogasawara B, Ogawa K, Hayashi H, Sassa H (1981) Plasma renin activity and plasma concentrations of norepinephrine and cyclic nucleotide in heart failure after prazosin. Clin Pharmacol Ther 29:464–471Google Scholar
  22. Pierce NF, Greenough WB, Carpenter CCJ (1971) Vibrio cholerae enterotoxin and its mode of action. Bacteriol Rev 35:1–13Google Scholar
  23. Sabol SL, Nirenberg M (1979) Regulation of adenylate cyclase of neuroblastoma x glioma hybrid cells by α-adrenergic receptors. J Biol Chem 254:1913–1920Google Scholar
  24. Schafer DE, Lust WD, Sircar B, Goldberg ND (1970) Elevated concentration of adenosine 3′:5′-cyclic monophosphate in intestinal mucosa after treatment with cholera toxin. Proc Natl Acad Sci USA 67:851–856Google Scholar
  25. Serebro HA, Iber FL, Yardley JH, Hendrix TR (1969) Inhibition of cholera toxin action in the rabbit by cycloheximide. Gastroenterology 56:506–511Google Scholar
  26. Sharp GWG, Hynie S (1971) Stimulation of intestinal adenylate cyclase by cholera toxin. Nature 229:266–269Google Scholar
  27. Starke K, Langer SZ (1979) A note on terminology for presynaptic receptors. In: Langer SZ, Starke K, Dubocovich ML (eds) Presynaptic receptors. Pergamon Press, Oxford, pp 1–3Google Scholar
  28. Tanaka T, Starke K (1979) Binding of 3H-clonidine to an α-adrenoceptor in membranes of guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 309:207–215Google Scholar
  29. Valiulis E, Long JF (1973) Effects of drugs on intestinal water secretion following cholera toxin in guinea pigs and rabbits. Physiologist 16:475Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Toshio Nakaki
    • 1
  • Teruo Nakadate
    • 1
  • Satoshi Yamamoto
    • 1
  • Ryuichi Kato
    • 1
  1. 1.Department of PharmacologyKeio University, School of MedicineTokyo 160Japan

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