The importance of delta and kappa opioid receptors in the property of thyrotropin-releasing hormone against hemorrhagic shock.
Many studies have demonstrated that thyrotropin-releasing hormone (TRH) produces various beneficial effects in the treatment of shock. TRH has been proposed to reverse the cardiovascular depression of endogenous opioid peptides. Nevertheless, it remains unknown whether opioid receptors are truly involved in this process. We designed experiments to study the importance of delta and kappa opioid receptors in the beneficial effects of TRH in hemorrhagic shock in rabbits and on opiate receptors following hemorrhagic shock in rats. The results indicated that TRH (50 micrograms, i.c.v.) significantly improved the mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and the maximal rate of ventricular systolic pressure changes (+/- dp/dtmax) during hemorrhagic shock in rabbits. This TRH effect was abolished by pretreatment with ICI174,864 (50 micrograms, i.c.v.), a highly selective delta opioid receptor antagonist, but not by pretreatment with nor-binaltorphimine (Nor-BNI, 50 micrograms, i.c.v.), a highly selective kappa opioid receptor antagonist. 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.) decreased the number (Bmax) of brain delta opioid receptors significantly, but it did not influence the receptor affinity. TRH did not influence the Bmax or affinity of brain kappa opioid receptors. These findings suggest that opioid receptors play an important role in mediating the antishock property of TRH. TRH-induced down-regulation of the number of brain opioid receptors may be one of the important mechanisms by which TRH exercises its protective effects in the treatment of shock.
Liu
L M
LM
Research Institute of Surgery, Daping Hospital, Chongqing, People's Republic of China.
Hu
D Y
DY
Chen
H S
HS
Lu
R Q
RQ
Yan
W
W
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011817:Rabbits; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D013973:Thyrotropin-Releasing Hormone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine