Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1978 Jul;63(3):519–527. doi: 10.1111/j.1476-5381.1978.tb07807.x

Effects of Cholinoceptor Antagonists on the Suckling-Induced and Experimentally Evoked Release of Oxytocin

G Clarke, Caroline HD Fall, DW Lincoln, Lynda P Merrick
PMCID: PMC1668097  PMID: 566601

Abstract

1 In the anaesthetized lactating rat, the suckling of the young causes the regular release (about every 7 min) of brief pulses of oxytocin (0.5 to 1.0 mu), which each produce a single transient increase in intramammary pressure.

2 The effects of several cholinoceptor antagonists were studied in relation to this natural reflex, and also the release of oxytocin evoked by the intraventricular injection of cholinomimetics.

3 Reflex milk ejection was blocked by the nicotinic antagonists mecamylamine and hexamethonium, and the inhibition was dose-dependent (ED50 of 1 mg/kg i.v. and 5 mg/kg i.v., respectively). Despite the use of high doses, the muscarinic antagonists atropine (200 mg/kg), hyoscine (90 mg/kg) and benzhexol (30 mg/kg) all failed to prevent the reflex release of oxytocin.

4 Acetylcholine (20 to 100 μg), bethanechol (0.2 to 4.0 μg) and carbachol (0.01 to 0.2 μg) injected into the cerebral ventricals stimulated a sustained release of oxytocin, which produced multiple increases in intramammary pressure. Nicotine (200 μg) was relatively ineffective by this route.

5 The release of oxytocin by intraventricular bethanechol or carbachol was abolished by atropine (0.1 to 1.0 mg/kg) but not by mecamylamine (5 mg/kg) or hexamethonium (5 mg/kg).

6 None of the antagonists used significantly affected either the release of oxytocin following electrical stimulation of the neurohypophysis or the mammary sensitivity to endogenous or exogenous oxytocin.

7 The results suggest that the neural pathway controlling the reflex release of oxytocin during suckling in the rat contains a cholinergic component, which acts through nicotinic receptors. A second cholinergic pathway, of the muscarinic type, may also exist. The role of these two pathways is discussed.

Full text

PDF
519

Selected References

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

  1. ABRAHAMS V. C., PICKFORD M. Simultaneous observations on the rate of urine flow and spontaneous uterine movements in the dog, and their relationship to posterior lobe activity. J Physiol. 1954 Nov 29;126(2):329–346. doi: 10.1113/jphysiol.1954.sp005213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BISSET G. W., WALKER J. M. The effects of nicotine, hexamethonium and ethanol on the secretion of the antidiuretic and oxytocic hormones of the rat. Br J Pharmacol Chemother. 1957 Dec;12(4):461–467. doi: 10.1111/j.1476-5381.1957.tb00166.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bridges T. E., Hillhouse E. W., Jones M. T. The effect of dopamine on neurohypophysial hormone release in vivo and from the rat neural lobe and hypothalamus in vitro. J Physiol. 1976 Sep;260(3):647–666. doi: 10.1113/jphysiol.1976.sp011537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burn J. H., Truelove L. H., Burn I. Antidiuretic Action of Nicotine. Br Med J. 1945 Mar 24;1(4394):403–406. doi: 10.1136/bmj.1.4394.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CROSS B. A., HARRIS G. W. The role of the neurohypophysis in the milk-ejection reflex. J Endocrinol. 1952 Apr;8(2):148–161. doi: 10.1677/joe.0.0080148. [DOI] [PubMed] [Google Scholar]
  6. CURTIS D. R., PHILLIS J. W. The action of procaine and atropine on spinal neurones. J Physiol. 1960 Aug;153:17–34. doi: 10.1113/jphysiol.1960.sp006516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Castro de Souza E., Rocha E Silva M., Jr The release of vasopressin by nicotine: further studies on its site of action. J Physiol. 1977 Feb;265(2):297–311. doi: 10.1113/jphysiol.1977.sp011717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clarke G., Davies J. The effects of anti-Parkinson drugs on cortical neurones. Br J Pharmacol. 1973 Mar;47(3):465–475. [PMC free article] [PubMed] [Google Scholar]
  9. Dreifuss J. J., Kelly J. S. The activity of identified supraoptic neurones and their response to acetylcholine applied by iontophoresis. J Physiol. 1972 Jan;220(1):105–118. doi: 10.1113/jphysiol.1972.sp009697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FARQUHARSON M. E., JOHNSTON R. G. Antagonism of the effects of tremorine by tropine derivatives. Br J Pharmacol Chemother. 1959 Dec;14:559–566. doi: 10.1111/j.1476-5381.1959.tb00964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feldberg W., Guertzenstein P. G., Rocha e Silva M., Jr Vasopressin release by nicotine: the site of action. Br J Pharmacol. 1975 Aug;54(4):463–474. doi: 10.1111/j.1476-5381.1975.tb07592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. GROSVENOR C. E., TURNER C. W. Evidence for adrenergic and cholinergic components in milk let-down reflex in lactating rat. Proc Soc Exp Biol Med. 1957 Aug-Sep;95(4):719–722. doi: 10.3181/00379727-95-23342. [DOI] [PubMed] [Google Scholar]
  13. HARINGTON M., KINCAID-SMITH P., MILNE M. D. Pharmacology and clinical use of pempidine in the treatment of hypertension. Lancet. 1958 Jul 5;2(7036):6–11. doi: 10.1016/s0140-6736(58)90002-3. [DOI] [PubMed] [Google Scholar]
  14. Harris G. W., Manabe Y., Ruf K. B. A study of the parameters of electrical stimulation of unmyelinated fibres in the pituitary stalk. J Physiol. 1969 Jul;203(1):67–81. doi: 10.1113/jphysiol.1969.sp008850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Krnjević K., Phillis J. W. Pharmacological properties of acetylcholine-sensitive cells in the cerebral cortex. J Physiol. 1963 May;166(2):328–350. doi: 10.1113/jphysiol.1963.sp007107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuhn E. R., McCann S. M. Release of oxytocin and vasopressin in lactating rats after injection of carbachol into the third ventricle. Neuroendocrinology. 1971;8(1):48–58. doi: 10.1159/000121993. [DOI] [PubMed] [Google Scholar]
  17. Kühn E. R., McCann S. M. Injections of carbachol into the third ventricle and release of oxytocin and vasopressin in the lactating rat. Arch Int Pharmacodyn Ther. 1970 Jul;186(1):192–193. [PubMed] [Google Scholar]
  18. Lincoln D. W., Hill A., Wakerley J. B. The milk-ejection reflex of the rat: an intermittent function not abolished by surgical levels of anaesthesia. J Endocrinol. 1973 Jun;57(3):459–476. doi: 10.1677/joe.0.0570459. [DOI] [PubMed] [Google Scholar]
  19. Lincoln D. W., Wakerley J. B. Electrophysiological evidence for the activation of supraoptic neurones during the release of oxytocin. J Physiol. 1974 Oct;242(2):533–554. doi: 10.1113/jphysiol.1974.sp010722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lincoln D. W., Wakerley J. B. Factors governing the periodic activation of supraoptic and paraventricular neurosecretory cells during suckling in the rat. J Physiol. 1975 Sep;250(2):443–461. doi: 10.1113/jphysiol.1975.sp011064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Milton A. S., Paterson A. T. A microinjection study of the control of antidiuretic hormone release by the supraoptic nucleus of the hypothalamus in the cat. J Physiol. 1974 Sep;241(3):607–628. doi: 10.1113/jphysiol.1974.sp010674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moos F., Richard P. Rôle de la noradrénaline et de l'acétylcholine dans la libération d'ocytocine induite par des stimulations vaginale, vagale et mammaire. J Physiol (Paris) 1975 Nov;70(3):315–332. [PubMed] [Google Scholar]
  23. Moss R. L., Urban I., Cross B. A. Microelectrophoresis of cholinergic and aminergic drugs on paraventricular neurons. Am J Physiol. 1972 Aug;223(2):310–318. doi: 10.1152/ajplegacy.1972.223.2.310. [DOI] [PubMed] [Google Scholar]
  24. Oba T., Ota K., Yokoyama A. Inhibition of milk-ejection reflex in lactating rats by systemic administration and intracerebral implantation of atropine. Neuroendocrinology. 1971;7(2):116–126. doi: 10.1159/000121959. [DOI] [PubMed] [Google Scholar]
  25. Pickford M. The action of acetylcholine in the supraoptic nucleus of the chloralosed dog. J Physiol. 1947 Jul 31;106(3):264–270. doi: 10.1113/jphysiol.1947.sp004209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sladek C. D., Knigge K. M. Cholinergic stimulation of vasopressin release from the rat hypothalamo-neurohypophyseal system. Endocrinology. 1977 Aug;101(2):411–420. doi: 10.1210/endo-101-2-411. [DOI] [PubMed] [Google Scholar]
  27. Wakerley J. B., Lincoln D. W. The milk-ejection reflex of the rat: a 20- to 40-fold acceleration in the firing of paraventricular neurones during oxytocin release. J Endocrinol. 1973 Jun;57(3):477–493. doi: 10.1677/joe.0.0570477. [DOI] [PubMed] [Google Scholar]

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

RESOURCES