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. 1993 Feb;108(2):336–341. doi: 10.1111/j.1476-5381.1993.tb12806.x

Chloroethylclonidine: an irreversible agonist at prejunctional alpha 2-adrenoceptors in rat vas deferens.

R Bültmann 1, K Starke 1
PMCID: PMC1907999  PMID: 8095416

Abstract

1. The possibility that chloroethylclonidine (CEC) activates prejunctional alpha 2-adrenoceptors was studied in the isolated vas deferens of the rat. Tissues were stimulated electrically and both the stimulation-evoked overflow of tritium (after preincubation with [3H]-noradrenaline) and the purinergic contraction component (isolated by prazosin 0.3 microM) were measured. 2. CEC (0.1-3 microM) concentration-dependently reduced the overflow of tritium evoked by trains of 6 pulses/100 Hz. The inhibition by CEC was not altered by prazosin (0.3 microM) but was prevented by pre-exposure to rauwolscine (0.3 microM). The inhibition, once established, did not fade upon washout of CEC, even when the washout fluid contained rauwolscine (0.3 microM). 3. CEC (0.1-3 microM) concentration-dependently reduced the purinergic component of contractions elicited by single pulses. The inhibition, again, was prevented by pre-exposure to rauwolscine (0.3 microM) and once established, did not fade upon washout of CEC, even when the washout fluid contained rauwolscine (0.3 microM). 4. CEC (3 microM) reduced the overflow of tritium evoked by 20 pulses/10 Hz, did not alter the overflow evoked by 100 pulses/10 Hz and increased the overflow evoked by 500 pulses/10 Hz. 5. CEC (3 microM) reduced the early peak, but increased the late plateau phase, of purinergic contractions elicited by 100 pulses/10 Hz. 6. It is concluded that CEC reduces the release of noradrenaline and a purinergic co-transmitter by irreversible activation of prejunctional alpha 2-adrenoceptors. CEC seems to be a partial alpha 2-agonist with an efficacy lower than that of noradrenaline. The prejunctional inhibitory effect limits the suitability of CEC for the characterization of postjunctional alpha 1-adrenoceptors mediating responses to sympathetic nerve stimulation.

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Selected References

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  1. Bourreau J. P., Zhang Z. D., Low A. M., Kwan C. Y., Daniel E. E. Ryanodine and the adrenergic, purinergic stimulation in the rat vas deferens smooth muscle: functional and radioligand binding studies. J Pharmacol Exp Ther. 1991 Mar;256(3):1063–1071. [PubMed] [Google Scholar]
  2. Brown D. A., Docherty J. R., French A. M., MacDonald A., McGrath J. C., Scott N. C. Separation of adrenergic and non-adrenergic contractions to field stimulation in the rat vas deferens. Br J Pharmacol. 1983 Jun;79(2):379–393. doi: 10.1111/j.1476-5381.1983.tb11010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burnstock G. The fifth Heymans memorial lecture-Ghent, February 17, 1990. Co-transmission. Arch Int Pharmacodyn Ther. 1990 Mar-Apr;304:7–33. [PubMed] [Google Scholar]
  4. Bültmann R., von Kügelgen I., Starke K. Contraction-mediating alpha 2-adrenoceptors in the mouse vas deferens. Naunyn Schmiedebergs Arch Pharmacol. 1991 Jun;343(6):623–632. doi: 10.1007/BF00184294. [DOI] [PubMed] [Google Scholar]
  5. Cichini G., Lassmann H., Placheta P., Singer E. A. Effects of clonidine on the stimulation-evoked release of 3H-noradrenaline from superfused rat brain slices as a function of the biophase concentration. Temperature dependent widening of extracellular space. Naunyn Schmiedebergs Arch Pharmacol. 1986 May;333(1):36–42. doi: 10.1007/BF00569657. [DOI] [PubMed] [Google Scholar]
  6. Docherty J. R. The pharmacology of alpha 1- and alpha 2-adrenoceptors: evidence for and against a further subdivision. Pharmacol Ther. 1989;44(2):241–284. doi: 10.1016/0163-7258(89)90067-3. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. French A. M., Scott N. C. Evidence to support the hypothesis that ATP is a co-transmitter in rat vas deferens. Experientia. 1983 Mar 15;39(3):264–266. doi: 10.1007/BF01955295. [DOI] [PubMed] [Google Scholar]
  9. Hammond J. R., MacDonald W. F., White T. D. Evoked secretion of [3H]noradrenaline and ATP from nerve varicosities isolated from the myenteric plexus of the guinea pig ileum. Can J Physiol Pharmacol. 1988 Apr;66(4):369–375. doi: 10.1139/y88-062. [DOI] [PubMed] [Google Scholar]
  10. Johnson R. D., Minneman K. P. Differentiation of alpha 1-adrenergic receptors linked to phosphatidylinositol turnover and cyclic AMP accumulation in rat brain. Mol Pharmacol. 1987 Mar;31(3):239–246. [PubMed] [Google Scholar]
  11. Kobinger W. Rudolf Buchheim lecture. Drugs as tools in research on adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1986 Feb;332(2):113–123. doi: 10.1007/BF00511400. [DOI] [PubMed] [Google Scholar]
  12. Leclerc G., Rouot B., Schwartz J., Velly J., Wermuth C. G. Studies on some para-substituted clonidine derivatives that exhibit an alpha-adrenoceptor stimulant activity. Br J Pharmacol. 1980;71(1):5–9. doi: 10.1111/j.1476-5381.1980.tb10902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Limberger N., Trendelenburg A. U., Starke K. Pharmacological characterization of presynaptic alpha 2-autoreceptors in rat submaxillary gland and heart atrium. Br J Pharmacol. 1992 Sep;107(1):246–255. doi: 10.1111/j.1476-5381.1992.tb14494.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lohse M. J., Klotz K. N., Schwabe U. Agonist photoaffinity labeling of A1 adenosine receptors: persistent activation reveals spare receptors. Mol Pharmacol. 1986 Oct;30(4):403–409. [PubMed] [Google Scholar]
  15. Mallard N. J., Marshall R. W., Sithers A. J., Spriggs T. L. Separation of putative alpha 1A- and alpha 1B-adrenoceptor mediated components in the tension response of the rat vas deferens to electrical field stimulation. Br J Pharmacol. 1992 Mar;105(3):727–731. doi: 10.1111/j.1476-5381.1992.tb09046.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Medgett I. C., McCulloch M. W., Rand M. J. Partial agonist of clonidine on prejunctional and postjunctional alpha-adrenoceptors. Naunyn Schmiedebergs Arch Pharmacol. 1978 Oct;304(3):215–221. doi: 10.1007/BF00507961. [DOI] [PubMed] [Google Scholar]
  17. Minneman K. P., Han C., Abel P. W. Comparison of alpha 1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101. Mol Pharmacol. 1988 May;33(5):509–514. [PubMed] [Google Scholar]
  18. Msghina M., Mermet C., Gonon F., Stjärne L. Electrophysiological and electrochemical analysis of the secretion of ATP and noradrenaline from the sympathetic nerves in rat tail artery: effects of alpha 2-adrenoceptor agonists and antagonists and noradrenaline reuptake blockers. Naunyn Schmiedebergs Arch Pharmacol. 1992 Aug;346(2):173–186. doi: 10.1007/BF00165299. [DOI] [PubMed] [Google Scholar]
  19. Muramatsu I., Kigoshi S., Ohmura T. Subtypes of alpha 1-adrenoceptors involved in noradrenaline-induced contractions of rat thoracic aorta and dog carotid artery. Jpn J Pharmacol. 1991 Dec;57(4):535–544. doi: 10.1254/jjp.57.535. [DOI] [PubMed] [Google Scholar]
  20. Muramatsu I. Relation between adrenergic neurogenic contraction and alpha 1-adrenoceptor subtypes in dog mesenteric and carotid arteries and rabbit carotid arteries. Br J Pharmacol. 1991 Jan;102(1):210–214. doi: 10.1111/j.1476-5381.1991.tb12155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schwietert H. R., Gouw M. A., Wilhelm D., Wilffert B., van Zwieten P. A. The role of alpha 1-adrenoceptor subtypes in the phasic and tonic responses to phenylephrine in the longitudinal smooth muscle of the rat portal vein. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):463–471. doi: 10.1007/BF00169547. [DOI] [PubMed] [Google Scholar]
  22. Singer E. A. Transmitter release from brain slices elicited by single pulses: a powerful method to study presynaptic mechanisms. Trends Pharmacol Sci. 1988 Aug;9(8):274–276. doi: 10.1016/0165-6147(88)90004-1. [DOI] [PubMed] [Google Scholar]
  23. Smith K., Docherty J. R. Are the prejunctional alpha 2-adrenoceptors of the rat vas deferens and submandibular gland of the alpha 2A- or alpha 2D-subtype? Eur J Pharmacol. 1992 Aug 25;219(2):203–210. doi: 10.1016/0014-2999(92)90297-h. [DOI] [PubMed] [Google Scholar]
  24. Starke K., Montel H., Gayk W., Merker R. Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Alpha-sympathomimetic inhibition of Neurogenic vasoconstriction. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(2):133–150. doi: 10.1007/BF00501149. [DOI] [PubMed] [Google Scholar]
  25. Starke K. Presynaptic alpha-autoreceptors. Rev Physiol Biochem Pharmacol. 1987;107:73–146. [PubMed] [Google Scholar]
  26. Starke K. Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol. 1977;77:1–124. doi: 10.1007/BFb0050157. [DOI] [PubMed] [Google Scholar]
  27. Sulpizio A., Hieble J. P. Lack of a pharmacological distinction between alpha-1 adrenoceptors mediating intracellular calcium-dependent and independent contractions to sympathetic nerve stimulation in the perfused rat caudal artery. J Pharmacol Exp Ther. 1991 Jun;257(3):1045–1052. [PubMed] [Google Scholar]
  28. Tian W. N., Gupta S., Deth R. C. Species differences in chlorethylclonidine antagonism at vascular alpha-1 adrenergic receptors. J Pharmacol Exp Ther. 1990 May;253(2):877–883. [PubMed] [Google Scholar]
  29. von Kügelgen I., Starke K. Noradrenaline-ATP co-transmission in the sympathetic nervous system. Trends Pharmacol Sci. 1991 Sep;12(9):319–324. doi: 10.1016/0165-6147(91)90587-i. [DOI] [PubMed] [Google Scholar]

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