Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1979 Feb;65(2):249–256. doi: 10.1111/j.1476-5381.1979.tb07825.x

Comparison of pre-junctional α-adrenoceptors at the neuromuscular junction with vascular post-junctional α-receptors in cat skeletal muscle

E Malta, GA McPherson, C Raper
PMCID: PMC1668626  PMID: 216453

Abstract

1 Activation of pre-junctional α-adrenoceptors at the skeletal neuromuscular junction enhances acetylcholine release whereas activation of such receptors at autonomic nerve endings inhibits transmitter output. In the present study the characteristics of pre-junctional α-adrenoceptors at motor nerve terminals have been compared with post-junctional (vascular) α-adrenoceptors in the cat hind limb.

2 Reversal of partial (+)-tubocurarine blockade of contractions of the tibialis anterior muscle was used to monitor pre-junctional activity and increases in hindlimb vascular resistance to assess post-junctional actions at α-adrenoceptors.

3 Responses to intra-arterial injections of noradrenaline, adrenaline, phenylephrine, oxymetazoline, methoxamine and clonidine were monitored. Dose-response lines for all the compounds except clonidine were parallel. The latter agent produced only weak and inconsistent effects.

4 Ratios of the doses of the agents required to produce pre- and post-junctional effects indicated that oxymetazoline and adrenaline possessed some preferential activity at post-junctional sites, whereas the remaining agents were non-selective in their actions. If dose-ratios with respect to noradrenaline were compared at the two sites none of the compounds possessed a marked degree of selectivity.

5 In the presence of phentolamine or tolazoline, dose-response curves to the pre- and post-junctional effects of phenylephrine were shifted to a similar extent. Thymoxamine showed preferential activity as a pre-junctional α-receptor antagonist.

6 In comparing the results of this study with those of other authors, it is apparent that there are marked differences in the characteristics of pre-junctional α-receptors at the skeletal neuromuscular junction and at autonomic nerve endings. The pre- and post-junctional α-receptors in skeletal muscle show less divergence.

Full text

PDF
249

Selected References

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

  1. Andén N. E., Grabowska M., Strömbom U. Different alpha-adrenoreceptors in the central nervous system mediating biochemical and functional effects of clonidine and receptor blocking agents. Naunyn Schmiedebergs Arch Pharmacol. 1976;292(1):43–52. doi: 10.1007/BF00506488. [DOI] [PubMed] [Google Scholar]
  2. Beani L., Bianchi C., Crema A. The effect of catecholamines and sympathetic stimulation on the release of acetylcholine from the guinea-pig colon. Br J Pharmacol. 1969 May;36(1):1–17. doi: 10.1111/j.1476-5381.1969.tb08298.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beani L., Bianchi C., Giacomelli A., Tamberi F. Noradrenaline inhibition of acetylcholine release from guinea-pig brain. Eur J Pharmacol. 1978 Mar 15;48(2):179–193. doi: 10.1016/0014-2999(78)90327-8. [DOI] [PubMed] [Google Scholar]
  4. Bowman W. C., Nott M. W. Actions of sympathomimetic amines and their antagonists on skeletal muscle. Pharmacol Rev. 1969 Mar;21(1):27–72. [PubMed] [Google Scholar]
  5. Bowman W. C., Raper C. Effects of sympathomimetic amines on neuromuscular transmission. Br J Pharmacol Chemother. 1966 Aug;27(2):313–331. doi: 10.1111/j.1476-5381.1966.tb01665.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cubeddu L., Barnes E. M., Langer S. Z., Weiner N. Release of norepinephrine and dopamine-beta-hydroxylase by nerve stimulation. I. Role of neuronal and extraneuronal uptake and of alpha presynaptic receptors. J Pharmacol Exp Ther. 1974 Sep;190(3):431–450. [PubMed] [Google Scholar]
  7. Doxey J. C., Everitt J. Inhibitory effects of clonidine on responses to sympathetic nerve stimulation in the pithed rat. Br J Pharmacol. 1977 Dec;61(4):559–566. doi: 10.1111/j.1476-5381.1977.tb07548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Doxey J. C., Smith C. F., Walker J. M. Selectivity of blocking agents for pre-and postsynaptic alpha-adrenoceptors. Br J Pharmacol. 1977 May;60(1):91–96. doi: 10.1111/j.1476-5381.1977.tb16752.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Drew G. M. Effects of alpha-adrenoceptor agonists and antagonists on pre- and postsynaptically located alpha-adrenoceptors. Eur J Pharmacol. 1976 Apr;36(2):313–320. doi: 10.1016/0014-2999(76)90084-4. [DOI] [PubMed] [Google Scholar]
  10. Drew G. M. Pharmacological characterisation of the presynaptic alpha-adrenoceptor in the rat vas deferens. Eur J Pharmacol. 1977 Mar 21;42(2):123–130. doi: 10.1016/0014-2999(77)90351-x. [DOI] [PubMed] [Google Scholar]
  11. Drew G. M. Pharmacological characterization of presynaptic alpha-adrenoceptors which regulate-cholinergic activity in the guinea-pig ileum [proceedings]. Br J Pharmacol. 1977 Mar;59(3):513P–513P. [PMC free article] [PubMed] [Google Scholar]
  12. Dun N., Karczmar A. G. The presynaptic site of action of norepinephrine in the superior cervical ganglion of guinea pig. J Pharmacol Exp Ther. 1977 Feb;200(2):328–335. [PubMed] [Google Scholar]
  13. Haeusler G. Studies on the possible contribution of a peripheral presynaptic action of clonidine and dopamine to their vascular effects under in vivo conditions. Naunyn Schmiedebergs Arch Pharmacol. 1976 Dec;295(3):191–202. doi: 10.1007/BF00505086. [DOI] [PubMed] [Google Scholar]
  14. Hepburn E. R., Reynoldson J. A., Li D. M., Bentley G. A. Effects of clonidine on vascular responses in kidney and hindlimbs of cats. Clin Exp Pharmacol Physiol. 1976 Nov-Dec;3(6):609–613. doi: 10.1111/j.1440-1681.1976.tb00642.x. [DOI] [PubMed] [Google Scholar]
  15. Knoll J., Vizi E. S. Presynaptic inhibition of acetylcholine release by endogenous and exogenous noradrenaline at high rate of stimulation. Br J Pharmacol. 1970 Nov;40(3):554P–555P. [PMC free article] [PubMed] [Google Scholar]
  16. Kosterlitz H. W., Lydon R. J., Watt A. J. The effects of adrenaline, noradrenaline and isoprenaline on inhibitory alpha- and beta-adrenoceptors in the longitudinal muscle of the guinea-pig ileum. Br J Pharmacol. 1970 Jun;39(2):398–413. doi: 10.1111/j.1476-5381.1970.tb12903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kuba K. Effects of catecholamines on the neuromuscular junction in the rat diaphragm. J Physiol. 1970 Dec;211(3):551–570. doi: 10.1113/jphysiol.1970.sp009293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lands A. M., Arnold A., McAuliff J. P., Luduena F. P., Brown T. G., Jr Differentiation of receptor systems activated by sympathomimetic amines. Nature. 1967 May 6;214(5088):597–598. doi: 10.1038/214597a0. [DOI] [PubMed] [Google Scholar]
  19. Langer S. Z. Sixth gaddum memorial lecture, National Institute for Medical Research, Mill Hill, January 1977. Presynaptic receptors and their role in the regulation of transmitter release. Br J Pharmacol. 1977 Aug;60(4):481–497. doi: 10.1111/j.1476-5381.1977.tb07526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Paton W. D., Vizi E. S. The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969 Jan;35(1):10–28. doi: 10.1111/j.1476-5381.1969.tb07964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Vizi E. S. The inhibitory action of noradrenaline and adrenaline on release of acetylcholine from guinea-pig ileum longitudinal strips. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;259(2):199–200. doi: 10.1007/BF00537789. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES