THE IMPORTANCE OF DELTA-OPIOID 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 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.