Back to Search
Start Over
Involvement of protein kinase C in the adaptive changes of cholinergic neurons to sympathetic denervation in the guinea pig myenteric plexus.
- Source :
-
Life sciences [Life Sci] 2003 Oct 03; Vol. 73 (20), pp. 2641-54. - Publication Year :
- 2003
-
Abstract
- Supersensitivity to muscarinic, kappa- and mu-opioid agents modulating cholinergic neurons in the guinea pig colon develops after chronic sympathetic denervation. A possible role for protein kinase C (PKC) in contributing to development of these sensitivity changes was investigated. The PKC activator, phorbol-12-myristate-13-acetate (PMA), enhanced acetylcholine (ACh) overflow in preparations obtained from normal animals. The facilitatory effect of PMA was significantly reduced after prolonged exposure to the phorbol ester and by the PKC inhibitors, chelerythrine and calphostin C. Subsensitivity to the facilitatory effect of PMA developed after chronic sympathetic denervation. In this experimental condition, immunoblot analysis revealed reduced levels of PKC in myenteric plexus synaptosomes. The facilitatory effect of the muscarininc antagonist, scopolamine, on ACh overflow was significantly reduced by the phospolipase C (PLC) inhibitor, U73122, chelerythrine and calphostin C, both in normal and denervated animals. However, in both experimental groups, PLC antagonists and PKC antagonists did not affect the inhibitory effect of the muscarinic agonist, oxotremorine-M on ACh overflow. The inhibitory effects of U69593 (kappa-opioid receptor agonist) and DAMGO (mu-opioid receptor agonist) on ACh overflow significantly increased in the presence of U73122, chelerythrine and calphostin C in preparations obtained from normal animals, but not in those obtained from sympathetically denervated animals. These results indicate that activation of PKC enhances ACh release in the myenteric plexus of the guinea pig colon. At this level, chronic sympathetic denervation entails a reduced efficiency of the enzyme. In addition, PKC is involved in the inhibitory modulation of ACh release mediated by muscarinic-, kappa- and mu-opioid receptors, although with different modalities. Muscarinic receptors inhibit PKC activity, whereas kappa- and mu-opioid receptors increase PKC activity. Both the inhibitory and the facilitatory effect on PKC involve modulation of PLC activity. The possibility that the change in PKC activity represents one of the biochemical mechanisms at the basis of development of sensitivity changes to opioid and muscarinic agents after chronic sympathetic denervation is discussed.
- Subjects :
- Acetylcholine metabolism
Alkaloids
Analgesics, Opioid pharmacology
Animals
Benzophenanthridines
Colon drug effects
Colon innervation
Colon metabolism
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- pharmacology
Enzyme Inhibitors pharmacology
Guinea Pigs
Immunoblotting
In Vitro Techniques
Muscarinic Agonists pharmacology
Muscarinic Antagonists pharmacology
Naphthalenes pharmacology
Oxotremorine pharmacology
Phenanthridines pharmacology
Protein Kinase C antagonists & inhibitors
Receptors, Opioid, kappa agonists
Receptors, Opioid, mu agonists
Scopolamine pharmacology
Tubulin metabolism
Adaptation, Physiological physiology
Myenteric Plexus physiology
Neurons physiology
Parasympathetic Nervous System cytology
Parasympathetic Nervous System physiology
Protein Kinase C physiology
Sympathectomy
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 73
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 12967688
- Full Text :
- https://doi.org/10.1016/s0024-3205(03)00665-9