PMID- 2122900
OWN - NLM
STAT- MEDLINE
DCOM- 19901210
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 40
IP  - 9
DP  - 1990 Nov 1
TI  - The effect of chronic ritanserin and clorgyline administration on 5-HT2 receptor 
      linked inositol phospholipid hydrolysis.
PG  - 2111-6
AB  - We have previously shown that chronic administration of the 5-hydroxytryptamine 
      (5-HT) receptor antagonist, ritanserin (10 mg/kg/day) or the monoamine oxidase 
      type A inhibitor (MAOI), clorgyline (2 mg/kg/day), results in a reduction in 
      5-HT2 receptor number in rat cerebral cortex. This study investigates the effects 
      of acute and chronic ritanserin administration, on 5-HT2 receptor linked inositol 
      phospholipid hydrolysis in rat cortical slices and compares it with the effect of 
      a chronic clorgyline regimen. [3H]Myo-inositol (50 microCi) was used to label 
      inositol phospholipids. Their subsequent hydrolysis in the presence or absence of 
      5-HT was determined by the accumulation of [3H]myoinositol monophosphate 
      ([3H]InsP). Addition of 5 nM ritanserin to slices had no effect on basal or 5-HT 
      stimulated [3H]InsP accumulation whereas 100 nM ritanserin blocked the stimulated 
      response by 65%. Acutely, ritanserin (15 mg/kg i.p.) completely blocked 5-HT 
      stimulated [3H]InsP accumulation. Chronic ritanserin or clorgyline treatment had 
      no effect on basal levels of [3H]InsP accumulation compared to controls (mean 
      value 3125 +/- 298 dpm/mg protein). Ritanserin increased 5-HT stimulated [3H]InsP 
      accumulation at 1 microM, 100 microM and 1 mM 5-HT and this effect was 
      significant at 100 microM 5-HT. Clorgyline had no significant or consistent 
      effect on 5-HT stimulated [3H]InsP accumulation at 1 microM, 100 microM and 1 mM 
      5-HT. Thus the effects of both chronic clorgyline and ritanserin administration 
      on 5-HT2 linked inositol phospholipid hydrolysis do not correlate with their 
      effects on 5-HT2 receptor number (Bmax). The situation is further complicated 
      since ritanserin significantly increases phosphatidylinositol (PtdIns), 
      phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 
      4,5-bisphosphate (PtdIns(4,5)P2) labelling whereas clorgyline significantly 
      increases PtdIns and PtdIns4P labelling. The implications of this are discussed.
FAU - Twist, E C
AU  - Twist EC
AD  - Department of Neuroscience, Institute of Psychiatry, London, U.K.
FAU - Brammer, M J
AU  - Brammer MJ
FAU - Stephenson, J D
AU  - Stephenson JD
FAU - Corn, T H
AU  - Corn TH
FAU - Campbell, I C
AU  - Campbell IC
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 145TFV465S (Ritanserin)
RN  - 333DO1RDJY (Serotonin)
RN  - LYJ16FZU9Q (Clorgyline)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Clorgyline/*pharmacology
MH  - Hydrolysis/drug effects
MH  - Phosphatidylinositols/*metabolism
MH  - Piperidines/*pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, Serotonin/*drug effects/metabolism
MH  - Ritanserin
MH  - Serotonin/pharmacology
MH  - Serotonin Antagonists/*pharmacology
EDAT- 1990/11/01 00:00
MHDA- 1990/11/01 00:01
CRDT- 1990/11/01 00:00
PHST- 1990/11/01 00:00 [pubmed]
PHST- 1990/11/01 00:01 [medline]
PHST- 1990/11/01 00:00 [entrez]
AID - 0006-2952(90)90242-D [pii]
AID - 10.1016/0006-2952(90)90242-d [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1990 Nov 1;40(9):2111-6. doi: 10.1016/0006-2952(90)90242-d.