Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 Oct;98(2):429–436. doi: 10.1111/j.1476-5381.1989.tb12614.x

An examination of the putative sigma-receptor in the mouse isolated vas deferens.

C Kennedy 1, G Henderson 1
PMCID: PMC1854698  PMID: 2555009

Abstract

1. The effects of several ligands which interact with the sigma-binding site were studied on the electrically-evoked (0.1 Hz) neurogenic twitch contractions of the mouse isolated vas deferens. 2. (+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine [+)-3-PPP) (10(-8) - 10(-5) M), inhibited the neurogenic twitch contractions. This inhibitory action was unaffected by naloxone (10(-6)M), idazoxan (10(-6)M), cocaine (10(-6)M) or tyramine (10(-4)-3 x 10(-4)M), but was abolished by the dopamine D2-antagonist, sulpiride (10(-6)M). Therefore, in order to study the potentiating actions of sigma ligands, sulpiride (10(-6)M) was used to prevent any inhibitory actions mediated via dopamine D2-receptors. 3. In the presence of sulpiride (10(-6)M), haloperidol (10(-6)-10(-5)M), (+)-3-PPP (10(-6)-3 x 10(-4) M) and (+)-N-allyl-N-normetazocine [+)-SKF 10,047) (10(-5)-10(-4)M) each reversibly potentiated the neurogenic twitch contractions in a concentration-dependent manner. The rank order of potency was haloperidol greater than (+)-3-PPP greater than (+)-SKF 10,047. 4. The stereoisomers of 3-PPP displayed stereoselectivity with (+)-3-PPP being more potent than (-)-3-PPP. 5. At a concentration that did not potentiate the twitch contractions, (3 x 10(-7)M), haloperidol did not antagonize the potentiating action of (+)-3-PPP (3 x 10(-5)M). 6. 1,3-Di-O-tolyguanidine (DTG) (10(-8)-10(-5)M) had no effect on the amplitude of twitch contractions and did not affect the potentiating action of (+)-3-PPP (10(-5)-3 x 10(-5)M).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
429

Images in this article

432Figure 4
on p.432
433Figure 6
on p.433

Selected References

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

  1. Allcorn R. J., Cunnane T. C., Kirkpatrick K. Actions of alpha, beta-methylene ATP and 6-hydroxydopamine on sympathetic neurotransmission in the vas deferens of the guinea-pig, rat and mouse: support for cotransmission. Br J Pharmacol. 1986 Dec;89(4):647–659. doi: 10.1111/j.1476-5381.1986.tb11169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anis N. A., Berry S. C., Burton N. R., Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983 Jun;79(2):565–575. doi: 10.1111/j.1476-5381.1983.tb11031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bom A. H., Verdouw P. D., Saxena P. R. Carotid haemodynamics in pigs during infusions of 8-OH-DPAT: reduction in arteriovenous shunting is mediated by 5-HT1-like receptors. Br J Pharmacol. 1989 Jan;96(1):125–132. doi: 10.1111/j.1476-5381.1989.tb11792.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowen W. D., Kirschner B. N., Newman A. H., Rice K. C. Sigma receptors negatively modulate agonist-stimulated phosphoinositide metabolism in rat brain. Eur J Pharmacol. 1988 May 10;149(3):399–400. doi: 10.1016/0014-2999(88)90678-4. [DOI] [PubMed] [Google Scholar]
  5. Bowen W. D., Walker J. M., Yashar A. G., Matsumoto R. R., Walker F. O., Lorden J. F. Altered haloperidol-sensitive sigma receptors in the genetically dystonic (dt) rat. Eur J Pharmacol. 1988 Feb 16;147(1):153–154. doi: 10.1016/0014-2999(88)90647-4. [DOI] [PubMed] [Google Scholar]
  6. Campbell B. G., Bobker D. H., Leslie F. M., Mefford I. N., Weber E. Both the sigma receptor-specific ligand (+)3-PPP and the PCP receptor-specific ligand TCP act in the mouse vas deferens via augmentation of electrically evoked norepinephrine release. Eur J Pharmacol. 1987 Jun 26;138(3):447–449. doi: 10.1016/0014-2999(87)90487-0. [DOI] [PubMed] [Google Scholar]
  7. Dunn W. R., McGrath J. C., Wilson V. G. Expression of functional postjunctional alpha 2-adrenoceptors in rabbit isolated distal saphenous artery--a permissive role for angiotensin II? Br J Pharmacol. 1989 Feb;96(2):259–261. doi: 10.1111/j.1476-5381.1989.tb11810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferris R. M., Tang F. L., Chang K. J., Russell A. Evidence that the potential antipsychotic agent rimcazole (BW 234U) is a specific, competitive antagonist of sigma sites in brain. Life Sci. 1986 Jun 23;38(25):2329–2337. doi: 10.1016/0024-3205(86)90640-5. [DOI] [PubMed] [Google Scholar]
  9. Gibson A., Samini M. The effects of bromocriptine on pre-synaptic and post-synaptic alpha-adrenoceptors in the mouse vas deferens. J Pharm Pharmacol. 1979 Dec;31(12):826–830. doi: 10.1111/j.2042-7158.1979.tb13674.x. [DOI] [PubMed] [Google Scholar]
  10. Henderson G., Hughes J., Kosterlitz H. W. A new example of a morphine-sensitive neuro-effector junction: adrenergic transmission in the mouse vas deferens. Br J Pharmacol. 1972 Dec;46(4):764–766. doi: 10.1111/j.1476-5381.1972.tb06901.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hjorth S., Carlsson A., Wikström H., Lindberg P., Sanchez D., Hacksell U., Arvidsson L. E., Svensson U., Nilsson J. L. 3-PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors. Life Sci. 1981 Mar 16;28(11):1225–1238. doi: 10.1016/0024-3205(81)90448-3. [DOI] [PubMed] [Google Scholar]
  12. Hughes J., Kosterlitz H. W., Leslie F. M. Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics. Br J Pharmacol. 1975 Mar;53(3):371–381. doi: 10.1111/j.1476-5381.1975.tb07373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Largent B. L., Gundlach A. L., Snyder S. H. Pharmacological and autoradiographic discrimination of sigma and phencyclidine receptor binding sites in brain with (+)-[3H]SKF 10,047, (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine and [3H]-1-[1-(2-thienyl)cyclohexyl]piperidine. J Pharmacol Exp Ther. 1986 Aug;238(2):739–748. [PubMed] [Google Scholar]
  14. Largent B. L., Gundlach A. L., Snyder S. H. Psychotomimetic opiate receptors labeled and visualized with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4983–4987. doi: 10.1073/pnas.81.15.4983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Largent B. L., Wikström H., Snowman A. M., Snyder S. H. Novel antipsychotic drugs share high affinity for sigma receptors. Eur J Pharmacol. 1988 Oct 18;155(3):345–347. doi: 10.1016/0014-2999(88)90527-4. [DOI] [PubMed] [Google Scholar]
  16. Malouf A. T., Swearengen E., Chavkin C. Comparison of the actions of phencyclidine and sigma ligands on CA1 hippocampal pyramidal neurons in the rat. Neuropharmacology. 1988 Nov;27(11):1161–1170. doi: 10.1016/0028-3908(88)90012-3. [DOI] [PubMed] [Google Scholar]
  17. Martin W. R., Eades C. G., Thompson J. A., Huppler R. E., Gilbert P. E. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther. 1976 Jun;197(3):517–532. [PubMed] [Google Scholar]
  18. Matsumoto R. R., Walker J. M. Inhibition of rubral neurons by a specific ligand for sigma receptors. Eur J Pharmacol. 1988 Dec 6;158(1-2):161–165. doi: 10.1016/0014-2999(88)90268-3. [DOI] [PubMed] [Google Scholar]
  19. Sonders M. S., Keana J. F., Weber E. Phencyclidine and psychotomimetic sigma opiates: recent insights into their biochemical and physiological sites of action. Trends Neurosci. 1988 Jan;11(1):37–40. doi: 10.1016/0166-2236(88)90048-3. [DOI] [PubMed] [Google Scholar]
  20. Su T. P. Evidence for sigma opioid receptor: binding of [3H]SKF-10047 to etorphine-inaccessible sites in guinea-pig brain. J Pharmacol Exp Ther. 1982 Nov;223(2):284–290. [PubMed] [Google Scholar]
  21. Tam S. W. Naloxone-inaccessible sigma receptor in rat central nervous system. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6703–6707. doi: 10.1073/pnas.80.21.6703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vaupel D. B., Su T. P. Guinea-pig vas deferens preparation may contain both receptors and phencyclidine receptors. Eur J Pharmacol. 1987 Jul 2;139(1):125–128. doi: 10.1016/0014-2999(87)90507-3. [DOI] [PubMed] [Google Scholar]
  23. Walker J. M., Matsumoto R. R., Bowen W. D., Gans D. L., Jones K. D., Walker F. O. Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs. Neurology. 1988 Jun;38(6):961–965. doi: 10.1212/wnl.38.6.961. [DOI] [PubMed] [Google Scholar]
  24. Weber E., Sonders M., Quarum M., McLean S., Pou S., Keana J. F. 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8784–8788. doi: 10.1073/pnas.83.22.8784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zukin R. S., Zukin S. R. Demonstration of [3H]cyclazocine binding to multiple opiate receptor sites. Mol Pharmacol. 1981 Sep;20(2):246–254. [PubMed] [Google Scholar]

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

RESOURCES