PMID- 10397406
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20151119
IS  - 0952-3278 (Print)
IS  - 0952-3278 (Linking)
VI  - 60
IP  - 4
DP  - 1999 Apr
TI  - Role of centrally administered melatonin and inhibitors of COX and NOS in 
      LPS-induced hyperthermia and adipsia.
PG  - 249-53
AB  - In the present study we have examined the effect of centrally administered 
      non-steroidal anti-inflammatory drugs (NSAIDS), nitric oxide synthase (NOS) 
      inhibitor and melatonin on lipopolysaccharide (LPS)-induced hyperthermia and its 
      anti-dipsogenic effect. Intracerebroventricular (i.c.v.) administration of LPS 
      (100-200 ng/rat) induces a dose dependent elevation in body temperature and 
      decreases water consumption in 24 h water deprived rats. Coadministration of 
      NSAIDS (indomethacin and nimesulide: 10 nM/rat each) with LPS (100 ng) reversed, 
      whereas NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME: 10-20 
      microg/rat) enhanced LPS-induced hyperthermia. In contrast L-NAME reversed the 
      LPS-induced anti-dipsogenic effect in a dose dependent manner, whereas NSAIDS 
      showed no change in the effect of LPS. Further, centrally administered 
      prostaglandin E2 (PGE2, 0.5-1 microg/rat) produced hyperthermia without affecting 
      the drinking behavior, suggesting that two independent mechanisms operate in 
      LPS-induced hyperthermia and in the anti-dipsogenic effect. The pineal hormone 
      melatonin is known to inhibit cellular damage caused by LPS, produced dose 
      dependent (5-10 nM i.c.v.) inhibition of LPS-induced hyperthermia and adipsia, 
      but failed to reverse the PGE2-induced hyperthermia, shows reversal of 
      LPS-induced hyperthermia by melatonin is due to inhibition of prostaglandin 
      synthesis rather than antagonism of prostaglandin action. The overall study 
      reveals that inhibition of both NO and prostaglandin production by melatonin 
      might be responsible for its reversal of LPS-induced hyperthermia and adipsia.
FAU - Raghavendra, V
AU  - Raghavendra V
AD  - Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab 
      University, Chandigarh, India.
FAU - Agrewala, J N
AU  - Agrewala JN
FAU - Kulkarni, S K
AU  - Kulkarni SK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Scotland
TA  - Prostaglandins Leukot Essent Fatty Acids
JT  - Prostaglandins, leukotrienes, and essential fatty acids
JID - 8802730
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Sulfonamides)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - JL5DK93RCL (Melatonin)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - V4TKW1454M (nimesulide)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Body Temperature/drug effects
MH  - Cyclooxygenase Inhibitors/*pharmacology
MH  - Dinoprostone/pharmacology
MH  - Fever/chemically induced/*metabolism
MH  - Indomethacin/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Melatonin/*pharmacology
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfonamides/pharmacology
MH  - Thirst/drug effects
MH  - Time Factors
EDAT- 1999/07/09 00:00
MHDA- 1999/07/09 00:01
CRDT- 1999/07/09 00:00
PHST- 1999/07/09 00:00 [pubmed]
PHST- 1999/07/09 00:01 [medline]
PHST- 1999/07/09 00:00 [entrez]
AID - S0952-3278(99)90032-7 [pii]
AID - 10.1054/plef.1999.0032 [doi]
PST - ppublish
SO  - Prostaglandins Leukot Essent Fatty Acids. 1999 Apr;60(4):249-53. doi: 
      10.1054/plef.1999.0032.