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Mediation by Protein Kinases C and A of G(o)-Linked Slow Responses of Enteric Neurons to 5-HT
The Journal of neuroscience, v 17(3), pp 1011-1024
01 Feb 1997
PMID: 8994056
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Abstract
5-HT activates the peristaltic reflex and is the neurotransmitter of a subset of myenteric interneurons. Hyperpolarizing afterpotential (AH)/type 2 neurons respond to 5-HT with a long-lived depolarization that is caused by the inhibition of a Ca(2+)-activated K(+) conductance (gK(Ca)). This effect is mediated by a G-protein-coupled receptor, 5-HT(1P). 5-HT(1P) agonists specifically activate Gα(o), the immunoreactivity of which was found to be highly abundant and membrane-associated in almost all enteric neurons. Responses of hyperpolarizing AH/type 2 neurons to 5-HT were inhibited by intracellular injection of GDPβS or anti-Gα(o) Fab fragments but were potentiated and prolonged by intracellular GTPγS. Responses to 5-HT were antagonized by pertussis toxin, downregulation of protein kinase C (PKC) and inhibitors of phosphatidylcholine phospholipase C (PC-PLC), PKC (including pseudosubstrate peptides, chelerythrine, and the α/β isoform-specific inhibitor G(ö) 6976), protein kinase A (PKA), and adenylate cyclase. Responses to 5-HT were mimicked by activators of PKC, and 5-HT induced a concentration-dependent increase in the membrane-associated PKC activity in isolated myenteric ganglia. Immunocytochemical studies suggested that the most abundant isoforms of PKC in enteric neurons are α and δ. These data suggest that signal transduction of the 5-HT(1P)-mediated slow response to 5-HT involves activation of PC-PLC by Gα(o) to liberate diacylglycerol, which stimulates PKC (most likely α). PKC probably activates adenylate cyclase, which through cAMP, activates PKA. Activation of both PKA and PKC lead to closure of gK(Ca).
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Details
- Title
- Mediation by Protein Kinases C and A of G(o)-Linked Slow Responses of Enteric Neurons to 5-HT
- Creators
- Hui Pan - Columbia UniversityHoau-Yan Wang - Allegheny University of the Health SciencesEitan Friedman - Allegheny University of the Health SciencesMichael D. Gershon - Columbia University
- Publication Details
- The Journal of neuroscience, v 17(3), pp 1011-1024
- Publisher
- Society for Neuroscience
- Resource Type
- Other
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:A1997WJ67800015
- Scopus ID
- 2-s2.0-0031036031
- Other Identifier
- 991019168610104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences