Lm. Liu et al., THE IMPORTANCE OF DELTA-OPIOID AND KAPPA-OPIOID RECEPTORS IN THE PROPERTY OF THYROTROPIN-RELEASING HORMONE AGAINST HEMORRHAGIC-SHOCK, Shock, 7(1), 1997, pp. 60-64
Many studies have demonstrated that thyrotropin-releasing hormone (TRH
) produces various beneficial effects in the treatment of shock, TRH h
as been proposed to reverse the cardiovascular depression of endogenou
s opioid peptides, Nevertheless, it remains unknown whether opioid rec
eptors are truely involved in this process, We designed experiments to
study the importance of delta and kappa opioid receptors in the benef
icial effects of TRH in hemorrhagic shock in rabbits and on opiate rec
eptors following hemorrhagic shock in rats. The results indicated that
TRH (50 mu g, i.c.v,) significantly improved the mean arterial pressu
re (MAP), left ventricular systolic pressure (LVSP), and the maximal r
ate of ventricular systolic pressure changes (+/-dp/dtmax) during hemo
rrhagic shock in rabbits, This TRH effect was abolished by pretreatmen
t with ICI174,864 (50 mu g, i.c.v.), a highly selective delta opioid r
eceptor antagonist, but not by pretreatment with nor-binaltorphimine (
Nor-BNI, 50 mu g, i.c.v.), a highly selective kappa opioid receptor an
tagonist, The maximal binding capacity (Bmax) of brain delta and kappa
opioid receptors significantly increased following hemorrhagic shock,
but the receptor affinity (Kd) did not change, TRH (5 mg/kg, i.v.) de
creased the number (Bmax) of brain delta opioid receptors significantl
y, but it did not influence the receptor affinity. TRH did not influen
ce the Bmax or affinity of brain kappa opioid receptors. These finding
s suggest that opioid receptors play an important role in mediating th
e antishock property of TRH. TRH-induced down-regulation of the number
of brain opioid receptors may be one of the important mechanisms by w
hich TRH exercises its protective effects in the treatment of shock.