Skip to main content
Log in

Presynaptic inhibitory actions of 2-substituted adenosine derivatives on neurotransmission in rat vas deferens: Effects of inhibitors of adenosine uptake and deamination

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

Summary

In the isolated rat vas deferens, various 2-substituted adenosine derivatives and adenosine inhibited contractions elicited by field stimulation but had little effect on responses to exogenous noradrenaline. 2-Chloroadenosine, 2-bromoadenosine, 2-hydroxyadenosine and 2-fluoroadenosine were all more potent than adenosine. Theophylline antagonized the action of the 2-substituted derivatives. The inhibitory action of adenosine was potentiated by dipyridamole, 2-amino-6-[(2-hydroxy-5-nitro)benzylthio]-9-β-d-ribofuranosylpurine (HNBTG) or 2′-deoxycoformycin while that of 2-chloroadenosine was not altered by any of these drugs or by phenoxybenzamine, atropine or indomethacin. Pretreatment of the vas deferens with both HNBTG and 2′-deoxycoformycin eliminated the difference in inhibitory potency between adenosine and 2-chloroadenosine.

These results indicate that 2-substituted adenosine derivatives, like adenosine, produce inhibition of transmission by acting on a presynaptic site which can be blocked by theophylline. The high apparent potency of 2-chloroadenosine compared to adenosine appears to be duc to the former being neither taken up nor deaminated, while the apparent potency of adenosine is masked by uptake and deamination in this tissue.

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

Access this article

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

References

  • Baer, H. P., Drummond, G. I.: Catabolism of adenine nucleotides by the isolated perfused rat heart. Proc. Soc. Exp. Biol. Med. 127, 33–36 (1968)

    Google Scholar 

  • Berlin, R. D., Oliver, J. A.: Membrane transport of purine and pyrimidine bases and nucleosides in animal cells. Int. Rev. Cytol. 42, 287–336 (1975)

    Google Scholar 

  • Burnstock, G.: Purinergic transmission. In: Handbook of psychopharmacology (Iversen, L. L. Iversen, S. D., Snyder, S. H. eds.), vol. 5, pp. 131–194. New York: Plenum Press 1975

    Google Scholar 

  • Cass, C. E., Au-Yeung, T. H.: Enhancement of 9-β-D-arabinofuranosyladenine cytotoxicity to mouse leukemia L1210 in vitro by 2′-deoxycoformycin. Cancer Res. 36, 1486–1491 (1976)

    Google Scholar 

  • Clanachan, A. S., Johns, A., Paton, D. M.: Presynaptic inhibitory actions of adenine nucleotides and adenosine on neurotransmission in the rat vas deferens. Neuroscience 2, 597–602 (1977)

    Google Scholar 

  • Clarke, D. A., Davoll, J., Phillips, F. S., Brown, G. B.: Enzymatic deamination and vasopressor effects of adenosine analogs. J. Pharmacol. Exp. Ther. 106, 291–302 (1952)

    Google Scholar 

  • Cobbin, L. B., Einstein, R., Maguire, M. H.: Studies on the coronary dilator actions of some adenosine analogues. Brit. J. Pharmacol. 50, 25–33 (1974)

    Google Scholar 

  • Enero, M. A., Saidman, B. Q.: Possible feed-back inhibition of noradrenaline release by purine compounds. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 39–46 (1977)

    Google Scholar 

  • Hedqvist, P.: Prostaglandin action on noradrenaline release and mechanical responses in the stimulated guinea-pig vas deferens. Acta Physiol. Scand. 90, 86–93 (1974)

    Google Scholar 

  • Hedqvist, P., Fredholm, B. B.: Effects of adenosine on adrenergic transmission; prejunctional inhibition and postjunctional enhancement. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 217–223 (1976)

    Google Scholar 

  • Illés, P., Hadházy, P., Torma, Z., Vizi, E. S., Knoll, J.: The effect of number of stimuli and rate of stimulation on the inhibition by PGE of adrenergic transmission. Eur. J. Pharmacol. 24, 29–36 (1973)

    Google Scholar 

  • Johns, D. G., Adamson, R. H.: Enhancement of the biological activity of cordycepin (3′deoxyadenosine) by the adenosine deaminase inhibitor 2′-deoxycoformycin. Biochem. Pharmacol. 25, 1441–1444 (1976)

    Google Scholar 

  • Kamikawa, Y., Shimo, Y.: Pharmacological differences of nonadrenergic inhibitory responses and of ATP-induced relaxation in guinea-pig trachea strip-chains. J. Pharm. Pharmacol. 28, 854–855 (1976)

    Google Scholar 

  • LePage, G. A., Worth, L. S., Kimball, A. P.: Enhancement of the anti-tumor activity of arabinofuranosyladenine by 2′-deoxycoformycin. Cancer Res. 36, 1481–1485 (1976)

    Google Scholar 

  • Muller, M. J., Paton, D. M.: Actions of 2-substituted adenosine derivatives on noradrenergic transmission in the rat vas deferens. Proc. Can. Fed. Biol. Soc. 20 (in press, 1978)

  • Needleman, P., Minkes, M. S., Douglas, J. R.: Stimulation of prostaglandin biosynthesis by adenine nucleotides. Circ. Res. 34, 455–460 (1974)

    Google Scholar 

  • Paton, D. M., Bär, H.-P., Clanachan, A. S., Lauzon, P. A.: Structure activity relations for inhibition of neurotransmission in rat vas deferens by adenosine. Neuroscience 3, 65–70 (1978)

    Google Scholar 

  • Plagemann, P. G. W.: Effect of temperature on the transport of nucleotides into Novikoff rat hepatoma cells growing in suspension culture. Arch. Biochem. Biophys. 140, 223–227 (1970)

    Google Scholar 

  • Rockwell, M., Maguire, M. H.: Studies on adenosine deaminase. 1. Purification and properties of ox heart adenosine deaminase. Mol. Pharmacol. 2, 574–584 (1966)

    Google Scholar 

  • Rowe, J. N., van Dyke, K., Westfall, D. P., Stitzel, R. E.: In vitro synthesis of ATP in guinea-pig vas deferens. Fed. Proc. 34, 739 (1975)

    Google Scholar 

  • Satchell, D. G., Burnstock, G.: Comparison of the inhibitory effects on the guinea-pig taenia coli of adenine nucleotides and adenosine in the presence and absence of dipyridamole. Eur. J. Pharmacol. 32, 324–328 (1975)

    Google Scholar 

  • Satchell, D. G., Maguire, M. H.: Inhibitory effects of adenine nucleotide analogs on the isolated guinea-pig taenia coli. J. Pharmacol. Exp. Ther. 195, 540–548 (1975)

    Google Scholar 

  • Schrader, J., Berne, R. M., Rubio, R.: Uptake and metabolism of adenosine by human erythrocyte ghosts. Am. J. Physiol. 223, 159–166 (1972)

    Google Scholar 

  • Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol. 77, 1–124 (1977)

    Google Scholar 

  • Su, C.: Purinergic inhibition of adrenergic transmission in rabbit blood vessels. J. Pharmacol. Exp. Ther. 204, 351–361 (1978)

    Google Scholar 

  • Swedin, G.: Studies on neurotransmission mechanism in the rat and guinea-pig vas deferens. Acta Physiol. Scand. Suppl. 369, 1–34 (1971)

    Google Scholar 

  • Verhaeghe, R. H., Vanhoutte, P. M., Shepherd, J. T.: Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides. Circ. Res. 40, 208–215 (1977)

    Google Scholar 

  • Westfall, T. C.: Local regulation of adrenergic neurotransmission. Physiol. Rev. 57, 659–728 (1977)

    Google Scholar 

  • Woo, P. W. K., Dion, H. W., Lange, S. M., Dahl, L. T., Durham, L. J.: A novel adenosine and ara-A deaminase inhibitor, (R)-3-(2-deoxy-β-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo [4,5-d] [1,3]diazepin-801. J. Heterocyclic. Chem. 11, 641–643 (1974)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muller, M.J., Paton, D.M. Presynaptic inhibitory actions of 2-substituted adenosine derivatives on neurotransmission in rat vas deferens: Effects of inhibitors of adenosine uptake and deamination. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 23–28 (1979). https://doi.org/10.1007/BF00515589

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00515589

Key words

Navigation