Muscarinic receptor regulation and protein kinase C: Sites for the action of chronic lithium in the hippocampus

R. H. Lenox, D. G. Watson, John Ellis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Regulation of muscarinic receptor activity in critical regions of the limbic system may represent a site for the therapeutic action of lithium. Muscarinic receptors in the hippocampus are coupled to phosphoinositide (PI) hydrolysis and the generation of the second messengers inositol (1,4,5) trisphosphate [Ins (1,4,5)P3] as well as diacylglycerol (DAG), which can directly activate protein kinase C (PKC). Since lithium may affect the regeneration of critical receptor-coupled pools of phosphatidylinositol 4,5-bisphosphate, studies in our laboratory have investigated the effects of chronic lithium on the regulation of the muscarinic receptor response. We have recently demonstrated that, following chronic administration of atropine in control and chronic lithium animals, there is an up-regulation of muscarinic receptor binding sites in the hippocampus; however, a concomitant sensitization of the carbachol-stimulated PI response is observed only in control animals. We have so far detected no effects of either in vitro or in vivo lithium on muscarinic receptor interactions with G proteins. However, we have observed a reduction in the in vitro phosphorylation of a major PKC phosphoprotein substrate in the rat hippocampus, following chronic lithium treatment. This effect may be related to long-lasting changes in regulation of receptor activity.

Original languageEnglish (US)
Pages (from-to)191-197
Number of pages7
JournalPsychopharmacology Bulletin
Volume27
Issue number3
StatePublished - 1991

Fingerprint

Lithium
Protein Kinase C
Muscarinic Receptors
Hippocampus
Phosphatidylinositols
Limbic System
Inositol 1,4,5-Trisphosphate
Phosphoproteins
Diglycerides
Carbachol
Second Messenger Systems
Atropine
GTP-Binding Proteins
muscarinic receptor kinase
Regeneration
Hydrolysis
Up-Regulation
Binding Sites
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Pharmacology

Cite this

@article{912530fae25e4938a51d55bd7c89a9b5,
title = "Muscarinic receptor regulation and protein kinase C: Sites for the action of chronic lithium in the hippocampus",
abstract = "Regulation of muscarinic receptor activity in critical regions of the limbic system may represent a site for the therapeutic action of lithium. Muscarinic receptors in the hippocampus are coupled to phosphoinositide (PI) hydrolysis and the generation of the second messengers inositol (1,4,5) trisphosphate [Ins (1,4,5)P3] as well as diacylglycerol (DAG), which can directly activate protein kinase C (PKC). Since lithium may affect the regeneration of critical receptor-coupled pools of phosphatidylinositol 4,5-bisphosphate, studies in our laboratory have investigated the effects of chronic lithium on the regulation of the muscarinic receptor response. We have recently demonstrated that, following chronic administration of atropine in control and chronic lithium animals, there is an up-regulation of muscarinic receptor binding sites in the hippocampus; however, a concomitant sensitization of the carbachol-stimulated PI response is observed only in control animals. We have so far detected no effects of either in vitro or in vivo lithium on muscarinic receptor interactions with G proteins. However, we have observed a reduction in the in vitro phosphorylation of a major PKC phosphoprotein substrate in the rat hippocampus, following chronic lithium treatment. This effect may be related to long-lasting changes in regulation of receptor activity.",
author = "Lenox, {R. H.} and Watson, {D. G.} and John Ellis",
year = "1991",
language = "English (US)",
volume = "27",
pages = "191--197",
journal = "Psychopharmacology Bulletin",
issn = "0048-5764",
publisher = "MedWorks Media LLC",
number = "3",

}

Muscarinic receptor regulation and protein kinase C : Sites for the action of chronic lithium in the hippocampus. / Lenox, R. H.; Watson, D. G.; Ellis, John.

In: Psychopharmacology Bulletin, Vol. 27, No. 3, 1991, p. 191-197.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Muscarinic receptor regulation and protein kinase C

T2 - Sites for the action of chronic lithium in the hippocampus

AU - Lenox, R. H.

AU - Watson, D. G.

AU - Ellis, John

PY - 1991

Y1 - 1991

N2 - Regulation of muscarinic receptor activity in critical regions of the limbic system may represent a site for the therapeutic action of lithium. Muscarinic receptors in the hippocampus are coupled to phosphoinositide (PI) hydrolysis and the generation of the second messengers inositol (1,4,5) trisphosphate [Ins (1,4,5)P3] as well as diacylglycerol (DAG), which can directly activate protein kinase C (PKC). Since lithium may affect the regeneration of critical receptor-coupled pools of phosphatidylinositol 4,5-bisphosphate, studies in our laboratory have investigated the effects of chronic lithium on the regulation of the muscarinic receptor response. We have recently demonstrated that, following chronic administration of atropine in control and chronic lithium animals, there is an up-regulation of muscarinic receptor binding sites in the hippocampus; however, a concomitant sensitization of the carbachol-stimulated PI response is observed only in control animals. We have so far detected no effects of either in vitro or in vivo lithium on muscarinic receptor interactions with G proteins. However, we have observed a reduction in the in vitro phosphorylation of a major PKC phosphoprotein substrate in the rat hippocampus, following chronic lithium treatment. This effect may be related to long-lasting changes in regulation of receptor activity.

AB - Regulation of muscarinic receptor activity in critical regions of the limbic system may represent a site for the therapeutic action of lithium. Muscarinic receptors in the hippocampus are coupled to phosphoinositide (PI) hydrolysis and the generation of the second messengers inositol (1,4,5) trisphosphate [Ins (1,4,5)P3] as well as diacylglycerol (DAG), which can directly activate protein kinase C (PKC). Since lithium may affect the regeneration of critical receptor-coupled pools of phosphatidylinositol 4,5-bisphosphate, studies in our laboratory have investigated the effects of chronic lithium on the regulation of the muscarinic receptor response. We have recently demonstrated that, following chronic administration of atropine in control and chronic lithium animals, there is an up-regulation of muscarinic receptor binding sites in the hippocampus; however, a concomitant sensitization of the carbachol-stimulated PI response is observed only in control animals. We have so far detected no effects of either in vitro or in vivo lithium on muscarinic receptor interactions with G proteins. However, we have observed a reduction in the in vitro phosphorylation of a major PKC phosphoprotein substrate in the rat hippocampus, following chronic lithium treatment. This effect may be related to long-lasting changes in regulation of receptor activity.

UR - http://www.scopus.com/inward/record.url?scp=0026091673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026091673&partnerID=8YFLogxK

M3 - Article

C2 - 1775588

AN - SCOPUS:0026091673

VL - 27

SP - 191

EP - 197

JO - Psychopharmacology Bulletin

JF - Psychopharmacology Bulletin

SN - 0048-5764

IS - 3

ER -