PMID- 8450499
OWN - NLM
STAT- MEDLINE
DCOM- 19930415
LR  - 20191101
IS  - 0197-5110 (Print)
IS  - 0197-5110 (Linking)
VI  - 13
IP  - 1-4
DP  - 1993
TI  - Muscarinic receptor regulation and 2nd messenger responses in rat neocortex 
      cultures.
PG  - 437-51
AB  - Primary cultures of dissociated cerebral cortex cells were used to characterize 
      the muscarinic acetylcholinergic receptors (mAChR) present and to study receptor 
      down-regulation and receptor mediated 2nd messenger responses induced by 
      muscarinic agonists. Binding of the hydrophilic antagonist [3H]N-methyl 
      scopolamine ([3H]NMS) to the cultured cells was saturated after one hour at 4 
      degrees C with a Kd of 93 pM and a Bmax of 958 fmol/mg protein. Competition 
      binding studies with several antagonists and agonists indicated that the mAChR 
      present in the culture were of a mixed M1/M3 subtype. The number of muscarinic 
      receptors at the cell surface decreased by 60% after one hour pre-incubation of 
      the cultures with 10 microM carbachol or oxotremorine. After down-regulation with 
      carbachol affinity for pirenzepine was decreased, while low affinity sites for 
      4-DAMP were lost, indicating that especially M1 subtypes are sensitive to this 
      type of regulation. Carbachol and oxotremorine-M induced a 2-3 fold increase in 
      phosphatidyl inositide (PI) turnover, which was blocked with high affinity by 
      both pirenzepine and 4-DAMP. Down-regulation of the mAChR and stimulation of 
      PI-turnover by agonists with different potency and intrinsic activity appeared 
      highly correlated. These data suggest that activation of the PI second-messenger 
      system is involved in the desensitization and down-regulation of the muscarinic 
      acetylcholine receptor.
FAU - van Huizen, F
AU  - van Huizen F
AD  - Organon Intl. B.V., Dept. of Neuropharmacology, Oss, The Netherlands.
FAU - Tonnaer, J A
AU  - Tonnaer JA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Recept Res
JT  - Journal of receptor research
JID - 8008358
RN  - 0 (Parasympatholytics)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Muscarinic)
RN  - 3G0285N20N (Pirenzepine)
RN  - 5RY0UWH1JL (Oxotremorine)
RN  - 81405-11-0 (4-diphenylacetoxy-1,1-dimethylpiperidinium)
RN  - 8Y164V895Y (Carbachol)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - Carbachol/pharmacology
MH  - Cells, Cultured
MH  - Cerebral Cortex/*drug effects/embryology
MH  - Down-Regulation
MH  - Oxotremorine/pharmacology
MH  - Parasympatholytics/pharmacology
MH  - Piperidines/pharmacology
MH  - Pirenzepine/pharmacology
MH  - Rats
MH  - Receptors, Muscarinic/*drug effects
MH  - Second Messenger Systems/*drug effects
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.3109/10799899309073671 [doi]
PST - ppublish
SO  - J Recept Res. 1993;13(1-4):437-51. doi: 10.3109/10799899309073671.