Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Aug;92(2):1068–1072. doi: 10.1172/JCI116611

A circulating substance cross-reacting with antiimidazoline antibodies. Detection in serum in relation to essential hypertension.

M Dontenwill 1, A Molines 1, A Verdun 1, G Bricca 1, S Laurent 1, P Bousquet 1
PMCID: PMC294947  PMID: 8349788

Abstract

It has been shown in various mammal species that clonidine, a well known centrally acting hypotensive agent, acts through the activation of imidazoline receptors (IRs) in the nucleus reticularis lateralis (NRL) of the brainstem. Specific binding sites sensitive to imidazolines and insensitive to catecholamines have been detected in rat and bovine, as well as human brains. An endogenous ligand, other than catecholamines, should exist for these IRs. Such a ligand could play a role in the pathophysiology of human essential hypertension. Therefore, we developed two RIAs with polyclonal and monoclonal anticlonidine antibodies. These antibodies presented specificity spectra similar to that of the IRs: they bound imidazolines and not catecholamines at all. These RIAs were used to detect imidazoline-like immunoreactivity in the human serum. Immunoreactive substance was measured in 26 normotensive subjects' sera, and specificity of interaction between antibodies and sera was verified. None of the known endogenous substances tested so far were able to interact with the two antibodies. Immunoreactivity in 32 essential hypertensive patients' sera proved higher in approximately 30% of cases. Values of immunoreactivity positively correlated with the mean arterial pressure values. This study demonstrates the existence of an "imidazoline-like" immunoreactive substance in the human serum with high levels in some hypertensive patients.

Full text

PDF
1068

Selected References

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

  1. Arndts D., Rominger K. L. Isolierung von Metaboliten neuer Arzneimittel zur massenspektrometrischen Strukturaufklärung. Arzneimittelforschung. 1978;28(11A):1951–1960. [PubMed] [Google Scholar]
  2. Arndts D., Stähle H., Förster H. J. Development of a RIA for clonidine and its comparison with the reference methods. J Pharmacol Methods. 1981 Dec;6(4):295–307. doi: 10.1016/0160-5402(81)90069-3. [DOI] [PubMed] [Google Scholar]
  3. Bousquet P., Feldman J., Atlas D. An endogenous, non-catecholamine clonidine antagonist increases mean arterial blood pressure. Eur J Pharmacol. 1986 May 13;124(1-2):167–170. doi: 10.1016/0014-2999(86)90138-x. [DOI] [PubMed] [Google Scholar]
  4. Bousquet P., Feldman J., Bloch R., Schwartz J. The nucleus reticularis lateralis: a region highly sensitive to clonidine. Eur J Pharmacol. 1981 Jan 29;69(3):389–392. doi: 10.1016/0014-2999(81)90490-8. [DOI] [PubMed] [Google Scholar]
  5. Bousquet P., Feldman J., Schwartz J. Central cardiovascular effects of alpha adrenergic drugs: differences between catecholamines and imidazolines. J Pharmacol Exp Ther. 1984 Jul;230(1):232–236. [PubMed] [Google Scholar]
  6. Bricca G., Dontenwill M., Molines A., Feldman J., Belcourt A., Bousquet P. The imidazoline preferring receptor: binding studies in bovine, rat and human brainstem. Eur J Pharmacol. 1989 Mar 14;162(1):1–9. doi: 10.1016/0014-2999(89)90597-9. [DOI] [PubMed] [Google Scholar]
  7. Dontenwill M., Bricca G., Molines A., Bousquet P., Belcourt A. Production and characterization of anti-clonidine antibodies not cross-reacting with catecholamines. Eur J Pharmacol. 1988 May 10;149(3):249–255. doi: 10.1016/0014-2999(88)90655-3. [DOI] [PubMed] [Google Scholar]
  8. Dontenwill M., Molines A., Bricca G., Stutzman J., Kempf J., Belcourt A., Bousquet P. Production and characterization of an iminoimidazolidine specific monoclonal antibody using para-aminoclonidine as antigen. Life Sci. 1992;50(24):1859–1868. doi: 10.1016/0024-3205(92)90546-2. [DOI] [PubMed] [Google Scholar]
  9. Ernsberger P., Giuliano R., Willette R. N., Reis D. J. Role of imidazole receptors in the vasodepressor response to clonidine analogs in the rostral ventrolateral medulla. J Pharmacol Exp Ther. 1990 Apr;253(1):408–418. [PubMed] [Google Scholar]
  10. Ernsberger P., Meeley M. P., Mann J. J., Reis D. J. Clonidine binds to imidazole binding sites as well as alpha 2-adrenoceptors in the ventrolateral medulla. Eur J Pharmacol. 1987 Jan 28;134(1):1–13. doi: 10.1016/0014-2999(87)90125-7. [DOI] [PubMed] [Google Scholar]
  11. Farina P. R., Homon C. A., Chow C. T., Keirns J. J., Zavorskas P. A., Esber H. J. Radioimmunoassay for clonidine in human plasma and urine using a solid phase second antibody separation. Ther Drug Monit. 1985;7(3):344–350. doi: 10.1097/00007691-198507030-00020. [DOI] [PubMed] [Google Scholar]
  12. Jarrott B., Spector S. Disposition of clonidine in rats as determined by radioimmunoassay. J Pharmacol Exp Ther. 1978 Oct;207(1):195–202. [PubMed] [Google Scholar]
  13. Kreisberg G. A., Diamant S., Diamant Y. Z., Atlas D. Raised levels of an endogenous nonadrenergic substance in the serum of pregnancy-induced hypertension patients. Isr J Med Sci. 1987 Dec;23(12):1194–1197. [PubMed] [Google Scholar]
  14. McPherson G. A. Analysis of radioligand binding experiments. A collection of computer programs for the IBM PC. J Pharmacol Methods. 1985 Nov;14(3):213–228. doi: 10.1016/0160-5402(85)90034-8. [DOI] [PubMed] [Google Scholar]
  15. Meeley M. P., Hensley M. L., Ernsberger P., Felsen D., Reis D. J. Evidence for a bioactive clonidine-displacing substance in peripheral tissues and serum. Biochem Pharmacol. 1992 Aug 18;44(4):733–740. doi: 10.1016/0006-2952(92)90410-k. [DOI] [PubMed] [Google Scholar]
  16. Parini A., Coupry I., Graham R. M., Uzielli I., Atlas D., Lanier S. M. Characterization of an imidazoline/guanidinium receptive site distinct from the alpha 2-adrenergic receptor. J Biol Chem. 1989 Jul 15;264(20):11874–11878. [PubMed] [Google Scholar]
  17. Synetos D., Manolopoulos V. G., Atlas D., Pipili-Synetos E. Human plasma-derived material with clonidine displacing substance (CDS)-like properties contracts the isolated rat aorta. J Auton Pharmacol. 1991 Dec;11(6):343–351. doi: 10.1111/j.1474-8673.1991.tb00258.x. [DOI] [PubMed] [Google Scholar]
  18. Tibiriça E., Feldman J., Mermet C., Gonon F., Bousquet P. An imidazoline-specific mechanism for the hypotensive effect of clonidine: a study with yohimbine and idazoxan. J Pharmacol Exp Ther. 1991 Feb;256(2):606–613. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES