Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1986 Jul;376:439–450. doi: 10.1113/jphysiol.1986.sp016162

Effects of forskolin on electrical behaviour of myenteric neurones in guinea-pig small intestine.

P R Nemeth, J M Palmer, J D Wood, D H Zafirov
PMCID: PMC1182807  PMID: 2432235

Abstract

The actions of forskolin on electrical behaviour of myenteric neurones were investigated with intracellular recording methods in guinea-pig small intestine. The actions of forskolin were: membrane depolarization, increased input resistance, suppression of post-spike hyperpolarizing potentials and repetitive spike discharge. These effects occurred always in AH/Type 2 myenteric neurones and never in the cells classified as S/Type 1. Reversal potentials for the depolarizing effects were near the estimated potassium equilibrium potential. Analyses based on the 'constant field equation' indicated that the permeability ratios of K+ to other permeant ionic species were reduced by forskolin. Pretreatment of the neurones with a phosphodiesterase inhibitor potentiated the effects of forskolin. The results suggest that activation of adenylate cyclase by forskolin and subsequent elevation of intraneuronal adenosine 3',5'-phosphate (cyclic AMP) mimic slow synaptic excitation in AH/Type 2 myenteric neurones. They support the possibility that cyclic AMP functions as a second messenger in signal transduction which appears to involve closure of calcium-dependent K+ channels and other membrane changes that lead to depolarization and a dramatic increase in the excitability of the neurones.

Full text

PDF
439

Selected References

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

  1. Grafe P., Mayer C. J., Wood J. D. Synaptic modulation of calcium-dependent potassium conductance in myenteric neurones in the guinea-pig. J Physiol. 1980 Aug;305:235–248. doi: 10.1113/jphysiol.1980.sp013360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Hirst G. D., Holman M. E., Spence I. Two types of neurones in the myenteric plexus of duodenum in the guinea-pig. J Physiol. 1974 Jan;236(2):303–326. doi: 10.1113/jphysiol.1974.sp010436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hirst G. D., Johnson S. M., van Helden D. F. The calcium current in a myenteric neurone of the guinea-pig ileum. J Physiol. 1985 Apr;361:297–314. doi: 10.1113/jphysiol.1985.sp015647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hirst G. D., Johnson S. M., van Helden D. F. The slow calcium-dependent potassium current in a myenteric neurone of the guinea-pig ileum. J Physiol. 1985 Apr;361:315–337. doi: 10.1113/jphysiol.1985.sp015648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hirst G. D., Spence I. Calcium action potentials in mammalian peripheral neurones. Nat New Biol. 1973 May 9;243(123):54–56. [PubMed] [Google Scholar]
  6. Johnson S. M., Katayama Y., North R. A. Multiple actions of 5-hydroxytryptamine on myenteric neurones of the guinea-pig ileum. J Physiol. 1980 Jul;304:459–470. doi: 10.1113/jphysiol.1980.sp013336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Katayama Y., North R. A. Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature. 1978 Jul 27;274(5669):387–388. doi: 10.1038/274387a0. [DOI] [PubMed] [Google Scholar]
  8. Katayama Y., North R. A., Williams J. T. The action of substance P on neurons of the myenteric plexus of the guinea-pig small intestine. Proc R Soc Lond B Biol Sci. 1979 Nov 30;206(1163):191–208. doi: 10.1098/rspb.1979.0101. [DOI] [PubMed] [Google Scholar]
  9. Kilmer S. L., Carlsen R. C. Forskolin activation of adenylate cyclase in vivo stimulates nerve regeneration. Nature. 1984 Feb 2;307(5950):455–457. doi: 10.1038/307455a0. [DOI] [PubMed] [Google Scholar]
  10. Nemeth P. R., Ort C. A., Wood J. D. Intracellular study of effects of histamine on electrical behaviour of myenteric neurones in guinea-pig small intestine. J Physiol. 1984 Oct;355:411–425. doi: 10.1113/jphysiol.1984.sp015427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nemeth P. R., Zafirov D. H., Wood J. D. Effects of cholecystokinin, caerulein and pentagastrin on electrical behavior of myenteric neurons. Eur J Pharmacol. 1985 Oct 22;116(3):263–269. doi: 10.1016/0014-2999(85)90161-x. [DOI] [PubMed] [Google Scholar]
  12. Nemeth P. R., Zafirov D., Wood J. D. Forskolin mimics slow synaptic excitation in myenteric neurons. Eur J Pharmacol. 1984 Jun 1;101(3-4):303–304. doi: 10.1016/0014-2999(84)90176-6. [DOI] [PubMed] [Google Scholar]
  13. Nishi S., North R. A. Intracellular recording from the myenteric plexus of the guinea-pig ileum. J Physiol. 1973 Jun;231(3):471–491. doi: 10.1113/jphysiol.1973.sp010244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. North R. A. The calcium-dependent slow after-hyperpolarization in myenteric plexus neurones with tetrodotoxin-resistant action potentials. Br J Pharmacol. 1973 Dec;49(4):709–711. doi: 10.1111/j.1476-5381.1973.tb08550.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Palmer J. M., Wood J. D., Zafirov D. H. Elevation of adenosine 3',5'-phosphate mimics slow synaptic excitation in myenteric neurones of the guinea-pig. J Physiol. 1986 Jul;376:451–460. doi: 10.1113/jphysiol.1986.sp016163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Seamon K. B., Daly J. W. Forskolin: a unique diterpene activator of cyclic AMP-generating systems. J Cyclic Nucleotide Res. 1981;7(4):201–224. [PubMed] [Google Scholar]
  17. Wood J. D. Enteric neurophysiology. Am J Physiol. 1984 Dec;247(6 Pt 1):G585–G598. doi: 10.1152/ajpgi.1984.247.6.G585. [DOI] [PubMed] [Google Scholar]
  18. Wood J. D., Mayer C. J. Adrenergic inhibition of serotonin release from neurons in guinea pig Auerback's plexus. J Neurophysiol. 1979 Mar;42(2):594–603. doi: 10.1152/jn.1979.42.2.594. [DOI] [PubMed] [Google Scholar]
  19. Wood J. D., Mayer C. J. Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel. J Neurophysiol. 1979 Mar;42(2):582–593. doi: 10.1152/jn.1979.42.2.582. [DOI] [PubMed] [Google Scholar]
  20. Zafirov D. H., Palmer J. M., Nemeth P. R., Wood J. D. Bombesin, gastrin releasing peptide and vasoactive intestinal peptide excite myenteric neurons. Eur J Pharmacol. 1985 Sep 10;115(1):103–107. doi: 10.1016/0014-2999(85)90590-4. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES