Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine

S J B Butt, R M Pitman

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Ionotropic nicotinic acetylcholine (ACh) receptors have been shown to be modulated by protein kinase-mediated phosphorylation in vitro. Here we demonstrate that 5-hydroxytryptamine (5-HT) can downregulate postsynaptic nicotinic ACh responses, elicited in an identified arthropod motoneuron in situ, by a mechanism dependent on protein kinase activity. Serotonergic modulation can be mimicked by perfusion with membrane-permeable analogues of either adenine (cAMP) or guanine (cGMP) cyclic nucleotides, and is prolonged in the presence of phosphodiesterase inhibitors. Furthermore, suppression of the ACh response by 5-HT is blocked by specific competitive inhibitors of protein kinase A and G, as well as the broad specificity protein kinase inhibitor staurosporine. The protein phosphatase inhibitor cantharidin similarly blocks recovery of the ACh response from suppression mediated by 5-HT. Thus, it appears that the nicotinic ACh response is modulated by a cAMP-mediated phosphorylation-dependent intracellular signalling pathway that is distinct from the direct block of mammalian nicotinic ACh receptors by 5-HT previously reported in vitro.

Original languageEnglish
Pages (from-to)1181-1188
Number of pages8
JournalEuropean Journal of Neuroscience
Volume21
DOIs
Publication statusPublished - Mar 2005

Keywords

  • ACh
  • cyclic nucleotide
  • protein kinase
  • serotonin
  • GATED ION CHANNELS
  • COCKROACH PERIPLANETA-AMERICANA
  • PROTEIN-KINASE
  • NITRIC-OXIDE
  • SYNAPTIC PLASTICITY
  • RECEPTOR
  • AMP
  • SEROTONIN
  • CALCIUM
  • NEURONS

Fingerprint

Dive into the research topics of 'Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine'. Together they form a unique fingerprint.

Cite this