Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine.
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, b...
| मुख्य लेखकों: | , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
2005
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| _version_ | 1826302722387738624 |
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| author | Butt, S Pitman, R |
| author_facet | Butt, S Pitman, R |
| author_sort | Butt, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:51:52Z |
| format | Journal article |
| id | oxford-uuid:e928b3f0-a365-410c-ab69-f5faac4eec69 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:51:52Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:e928b3f0-a365-410c-ab69-f5faac4eec692022-03-27T10:52:13ZIndirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e928b3f0-a365-410c-ab69-f5faac4eec69EnglishSymplectic Elements at Oxford2005Butt, SPitman, RIonotropic 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. |
| spellingShingle | Butt, S Pitman, R Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title | Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title_full | Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title_fullStr | Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title_full_unstemmed | Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title_short | Indirect phosphorylation-dependent modulation of postsynaptic nicotinic acetylcholine responses by 5-hydroxytryptamine. |
| title_sort | indirect phosphorylation dependent modulation of postsynaptic nicotinic acetylcholine responses by 5 hydroxytryptamine |
| work_keys_str_mv | AT butts indirectphosphorylationdependentmodulationofpostsynapticnicotinicacetylcholineresponsesby5hydroxytryptamine AT pitmanr indirectphosphorylationdependentmodulationofpostsynapticnicotinicacetylcholineresponsesby5hydroxytryptamine |