Journal article
Pharmacological investigations of the cellular transduction pathways used by cholecystokinin to activate nodose neurons
Autonomic neuroscience, Vol.164(1-2), pp.20-26
10/28/2011
Handle:
https://hdl.handle.net/2376/111339
PMCID: PMC3167007
PMID: 21664195
Abstract
Cholecystokinin (CCK) directly activates vagal afferent neurons resulting in coordinated gastrointestinal functions and satiation. In vitro, the effects of CCK on dissociated vagal afferent neurons are mediated via activation of the vanilloid family of transient receptor potential (TRPV) cation channels leading to membrane depolarization and an increase in cytosolic calcium. However, the cellular transduction pathway(s) involved in this process between CCK receptors and channel opening have not been identified. To address this question, we monitored CCK-induced cytosolic calcium responses in dissociated nodose neurons from rat in the presence or absence of reagents that interact with various intracellular signaling pathways. We found that the phospholipase C (PLC) inhibitor U-73122 significantly attenuated CCK-induced responses, whereas the inactive analog U-73433 had no effect. Responses to CCK were also cross-desensitized by a brief pretreatment with m-3M3FBS, a PLC stimulator. Together these observations strongly support the participation of PLC in the effects of CCK on vagal afferent neurons. In contrast, pharmacological antagonism of phospholipase A2, protein kinase A, and phosphatidylinositol 3-kinase revealed that they are not critical in the CCK-induced calcium response in nodose neurons. Further investigations of the cellular pathways downstream of PLC showed that neither protein kinase C (PKC) nor generation of diacylglycerol (DAG) or release of calcium from intracellular stores participates in the response to CCK. These results suggest that alteration of membrane phosphatidylinositol 4,5-bisphosphate (PIP2) content by PLC activity mediates CCK-induced calcium response and that this pathway may underlie the vagally-mediated actions of CCK to induce satiation and alter gastrointestinal functions.
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Details
- Title
- Pharmacological investigations of the cellular transduction pathways used by cholecystokinin to activate nodose neurons
- Creators
- Huan ZhaoDallas C KinchSteven M Simasko
- Publication Details
- Autonomic neuroscience, Vol.164(1-2), pp.20-26
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Elsevier B.V
- Identifiers
- 99900547431901842
- Language
- English
- Resource Type
- Journal article