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

Journal article

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.

Authors: Butt, S; Pitman, R

• Publication status: Published
• Journal: European journal of neuroscience
• Volume: 21
• Issue: 5
• Pages: 1181-1188
• Publication date: 2005-03-01
• DOI: 10.1111/j.1460-9568.2005.03947.x
• EISSN: 1460-9568
• ISSN: 0953-816X
• Language: English
• Keywords: Phosphorylation; Motor Neurons; Drug Interactions; Cyclic GMP; Male; Free Radical Scavengers; Patch-Clamp Techniques; Staurosporine; Synaptic Transmission; Serotonin; Theophylline; Electric Stimulation; Acetylcholine; Time Factors; Enzyme Inhibitors; Receptors, Nicotinic; Central Nervous System; Cyclic AMP; Membrane Potentials; Cockroaches; Animals