Interaction between norepinephrine and prostaglandin e2 in the
preoptic area of guinea pigs.
Sehic, Elmir, Alberte L. Ungar, and Clark M. Blatteis.
Department of Physiology and Biophysics, University of Tennessee,
Memphis, Memphis, Tennessee 38163
APStracts 3:0099R, 1996.
The release of norepinephrine (NE) and prostaglandin E2 (PGE2) in the
preoptic-anterior hypothalamus (POA) by systemically administered
pyrogens suggests that both substances may mediate the febrile
response. To investigate their possible interaction, we measured
directly the levels of PGE2 in the extracellular fluid of the POA of
conscious guinea pigs microdialyzed intrapreoptically with exogenous
NE over the entire course of their febrile response to endotoxin.
Acidified and buffered NE (NEa, NEb), artificial cerebrospinal fluid
(aCSFa, aCSFb), and vehicle (VEHa,VEHb) were tested. All but aCSFb
depressed the febrile response to endotoxin. The microdialysis of
aCSFa, aCSFb, VEHa, VEHb, and NEa did not change basal preoptic PGE2
levels. However, NEb, at a dose that by itself did not affect Tb,
caused a large elevation in preoptic PGE2. The iv injection of
endotoxin increased the level of PGE2 in the POA. NEb potentiated
this increase whereas NEa, aCSFa, and VEHb reduced it; VEHa reduced
it for the first 60 min and enhanced it for the last 90 min of the
experiment. Thus, these data suggest that the low pH of the NE solute
and/or its VEH may confound the observed effects of NE on the Tb and
preoptic PGE2 induced by endotoxin. We surmise that this is due to a
neurotoxic action of the antioxidants and the acidity of the solution
on thermosensitive neurons in the POA. Hence, the results of
experiments using exogenous, usually acidified NE preparations that
often also contain additives should be interpreted with caution.
Received 25 September 1995; accepted in final form 23 February
1996.
APS Manuscript Number R599-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96