Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1989 Feb;96(2):333–340. doi: 10.1111/j.1476-5381.1989.tb11822.x

Interactions of calcium antagonists and the calcium channel agonist Bay K 8644 on neurotransmission of the mouse isolated vas deferens.

G A Rae 1, J B Calixto 1
PMCID: PMC1854357  PMID: 2466518

Abstract

1. The present study compares the effects of verapamil and Bay K 8644 on twitches of the mouse vas deferens induced by field stimulation at 0.1 Hz. The influence of interactions between these drugs and nifedipine on neurotransmission was also investigated. 2. Bay K 8644 (0.1 nM-3 microM) and verapamil (1-100 microM) potentiated twitches maximally by about 1000% (EC50 17.3 nM) and 300% (EC50 17.5 microM), respectively. Nifedipine (0.1 nM-1 microM) only reduced twitch magnitude (IC50 7.7 nM). All effects were reversed following washout. 3. Yohimbine (1-100 microM) reversed twitch potentiation caused by verapamil but not by Bay K 8644. Prazosin (1 microM) did not reduce basal twitch tension nor antagonize twitch potentiation by verapamil. 4. Twitch inhibition by nifedipine was unaltered by previous incubation with verapamil (30 microM), but Bay K 8644 (1 microM) shifted the curve to nifedipine 120 fold to the right. Previous incubation with nifedipine (1 microM) blocked potentiation induced by verapamil but did not modify responsiveness to Bay K 8644. 5. Previous addition of verapamil (30 microM) markedly enhanced twitch potentiation caused by Bay K 8644 in a supra-additive fashion. In experiments conducted in the reversed condition, Bay K 8644 (1 nM but not 10 nM) potentiated the effect of verapamil in a similar manner but to a lesser extent. 6. It is concluded that verapamil, in contrast to nifedipine, markedly enhances neurally-evoked twitches of the mouse vas deferens. Bay K 8644 produces essentially the same effect as verapamil, but its potency is 1000 fold and its maximal effect about 3 fold greater than that observed for verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
335

Selected References

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

  1. Beattie D. T., Cunnane T. C., Muir T. C. Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea-pig vas deferens. Br J Pharmacol. 1986 Sep;89(1):235–244. doi: 10.1111/j.1476-5381.1986.tb11140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Daniell L. C., Barr E. M., Leslie S. W. 45Ca2+ uptake into rat whole brain synaptosomes unaltered by dihydropyridine calcium antagonists. J Neurochem. 1983 Nov;41(5):1455–1459. doi: 10.1111/j.1471-4159.1983.tb00845.x. [DOI] [PubMed] [Google Scholar]
  3. Forsyth K. M., Pollock D. Clonidine and morphine increase [3H]-noradrenaline overflow in mouse vas deferens. Br J Pharmacol. 1988 Jan;93(1):35–42. doi: 10.1111/j.1476-5381.1988.tb11402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Freedman S. B., Miller R. J. Calcium channel activation: a different type of drug action. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5580–5583. doi: 10.1073/pnas.81.17.5580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. French A. M., Scott N. C. A comparison of the effects of nifedipine and verapamil on rat vas deferens. Br J Pharmacol. 1981 Jun;73(2):321–323. doi: 10.1111/j.1476-5381.1981.tb10424.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Hay D. W., Wadsworth R. M. Local anaesthetic activity of organic calcium antagonists: relevance to their actions on smooth muscle. Eur J Pharmacol. 1982 Feb 5;77(4):221–228. doi: 10.1016/0014-2999(82)90122-4. [DOI] [PubMed] [Google Scholar]
  8. Hay D. W., Wadsworth R. M. The effects of calcium channel inhibitors on twitches and noradrenaline contractions of the rat bisected vas deferens. Eur J Pharmacol. 1983 Mar 4;87(4):367–378. doi: 10.1016/0014-2999(83)90075-4. [DOI] [PubMed] [Google Scholar]
  9. Jones M. E., Spriggs T. L. Noradrenaline and motor transmission in the vas deferens of the mouse. Br J Pharmacol. 1975 Mar;53(3):323–331. [PMC free article] [PubMed] [Google Scholar]
  10. Karaki H., Nakagawa H., Urakawa N. Effects of calcium antagonists on release of [3H]noradrenaline in rabbit aorta. Eur J Pharmacol. 1984 Jun 1;101(3-4):177–183. doi: 10.1016/0014-2999(84)90154-7. [DOI] [PubMed] [Google Scholar]
  11. Kingsbury A., Balazs R. Effect of calcium agonists and antagonists on cerebellar granule cells. Eur J Pharmacol. 1987 Aug 21;140(3):275–283. doi: 10.1016/0014-2999(87)90284-6. [DOI] [PubMed] [Google Scholar]
  12. Larsson B., Högestätt E. D., Mattiasson A., Andersson K. E. Differential effects of nifedipine, verapamil, and diltiazem on noradrenaline-induced contractions, adrenergic transmitter release, and alpha-adrenoceptor binding in the female rabbit urethra. Naunyn Schmiedebergs Arch Pharmacol. 1984 May;326(1):14–21. doi: 10.1007/BF00518773. [DOI] [PubMed] [Google Scholar]
  13. Marshall I., Nasmyth P. A., Shepperson N. B. The effects of release and depletion of endogenous noradrenaline on the transmission of impulses in the mouse vas deferens. Br J Pharmacol. 1978 Sep;64(1):145–151. doi: 10.1111/j.1476-5381.1978.tb08651.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Middlemiss D. N., Spedding M. A functional correlate for the dihydropyridine binding site in rat brain. Nature. 1985 Mar 7;314(6006):94–96. doi: 10.1038/314094a0. [DOI] [PubMed] [Google Scholar]
  15. Moritoki H., Iwamoto T., Kanaya J., Maeshiba Y., Ishida Y., Fukuda H. Verapamil enhances the non-adrenergic twitch response of rat vas deferens. Eur J Pharmacol. 1987 Aug 4;140(1):75–83. doi: 10.1016/0014-2999(87)90636-4. [DOI] [PubMed] [Google Scholar]
  16. Murphy K. M., Snyder S. H. Calcium antagonist receptor binding sites labeled with [3H]nitrendipine. Eur J Pharmacol. 1982 Jan 22;77(2-3):201–202. doi: 10.1016/0014-2999(82)90021-8. [DOI] [PubMed] [Google Scholar]
  17. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  18. Rae G. A., De Moraes S. Presynaptic alpha 2-adrenoceptor subsensitivity in the morphine-withdrawn mouse vas deferens. Eur J Pharmacol. 1984 Sep 17;104(3-4):261–266. doi: 10.1016/0014-2999(84)90401-1. [DOI] [PubMed] [Google Scholar]
  19. Rae G. A., De Moraes S. Supersensitivity to noradrenaline in vas deferens from morphine-dependent mice is confirmed. Eur J Pharmacol. 1983 Jan 21;86(3-4):347–352. doi: 10.1016/0014-2999(83)90183-8. [DOI] [PubMed] [Google Scholar]
  20. Rampe D., Janis R. A., Triggle D. J. BAY K 8644, a 1,4-dihydropyridine Ca2+ channel activator: dissociation of binding and functional effects in brain synaptosomes. J Neurochem. 1984 Dec;43(6):1688–1692. doi: 10.1111/j.1471-4159.1984.tb06096.x. [DOI] [PubMed] [Google Scholar]
  21. Spedding M. Assessment of "Ca2+ -antagonist" effects of drugs in K+ -depolarized smooth muscle. Differentiation of antagonist subgroups. Naunyn Schmiedebergs Arch Pharmacol. 1982 Feb;318(3):234–240. doi: 10.1007/BF00500485. [DOI] [PubMed] [Google Scholar]
  22. Spedding M. Competitive interactions between Bay K 8644 and nifedipine in K+ depolarized smooth muscle: a passive role for Ca2+? Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):464–466. doi: 10.1007/BF00692917. [DOI] [PubMed] [Google Scholar]
  23. Stjärne L., Lundberg J. M., Astrand P. Neuropeptide Y--a cotransmitter with noradrenaline and adenosine 5'-triphosphate in the sympathetic nerves of the mouse vas deferens? A biochemical, physiological and electropharmacological study. Neuroscience. 1986 May;18(1):151–166. doi: 10.1016/0306-4522(86)90184-3. [DOI] [PubMed] [Google Scholar]
  24. Stjärne L., Lundberg J. M. On the possible roles of noradrenaline, adenosine 5'-triphosphate and neuropeptide Y as sympathetic cotransmitters in the mouse vas deferens. Prog Brain Res. 1986;68:263–278. doi: 10.1016/s0079-6123(08)60243-5. [DOI] [PubMed] [Google Scholar]
  25. Taube J. S., Schwartzkroin P. A. Ineffectiveness of organic calcium channel blockers in antagonizing long-term potentiation. Brain Res. 1986 Aug 6;379(2):275–285. doi: 10.1016/0006-8993(86)90781-x. [DOI] [PubMed] [Google Scholar]
  26. Turner T. J., Goldin S. M. Calcium channels in rat brain synaptosomes: identification and pharmacological characterization. High affinity blockade by organic Ca2+ channel blockers. J Neurosci. 1985 Mar;5(3):841–849. doi: 10.1523/JNEUROSCI.05-03-00841.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Meel J. C., De Jonge A., Kalkman H. O., Wilffert B., Timmermans P. B., Van Zwieten P. A. Vascular smooth muscle contraction initiated by postsynaptic alpha 2-adrenoceptor activation is induced by an influx of extracellular calcium. Eur J Pharmacol. 1981 Jan 16;69(2):205–208. doi: 10.1016/0014-2999(81)90415-5. [DOI] [PubMed] [Google Scholar]
  28. Woodward J. J., Leslie S. W. Bay K 8644 stimulation of calcium entry and endogenous dopamine release in rat striatal synaptosomes antagonized by nimodipine. Brain Res. 1986 Apr 9;370(2):397–400. doi: 10.1016/0006-8993(86)90502-0. [DOI] [PubMed] [Google Scholar]
  29. Zetler G., Kaschube M. Importance of frequency and pulse with in field stimulation of the mouse vas deferens: different behaviour of twitch-inhibiting drugs. Naunyn Schmiedebergs Arch Pharmacol. 1985 Oct;331(1):82–88. doi: 10.1007/BF00498855. [DOI] [PubMed] [Google Scholar]
  30. Zsotér T. T., Wolchinsky C., Endrenyi L. Effects of verapamil on [3H]norepinephrine release. J Cardiovasc Pharmacol. 1984 Nov-Dec;6(6):1060–1066. [PubMed] [Google Scholar]

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

RESOURCES