The Analgesic Mechanisms And Cardiovascular Effects Of Chimeric Peptide MCRT

To elucidate the analgesic mechanisms and cardiovascular effects of the potent analgesic chimeric peptide MCRT in anesthetized rats,we have studied the analgesic mechanism of MCRT by in vitro experiments,pre-injection antagonists to MCRT and Morphiceptin and co-injection of the parent peptides.To get the effect of MCRT in the regulation to blood pressure we used the injections of intravenous(i.v.)and intracerebroventricular(i.c.v.),and naloxone and L-NAME were pre-injected before MCRT to get the mechanism.The results showed that MCRT has mixed ?/?opioid receptor angonist activity,it has potent analgesic because of the dual ligand function to mu and delta receptors.MCRT by intravenous and intracerebroventricular injection all induced bloodpressure lowering and bradycardiac,which was stronger than that of parent peptides.When co-injected MCRT and NPFF,it could dose-dependently weaken the cardiovascular effects of MCRT.As a result of naloxone completely abolished it's effects,opioid receptors involved in the bloodpressure regulation of MCRT no matter by intravenous injection or intracerebroventricular injection,and the effect on heartrate was also completely dependent on opioid receptors.However,the effect of MCRT by peripheral injection on heart rate had no relationship with opioid receptors.NO pathway is involved in the regulation of MCRT on blood pressure by both injection styles,but peripheral NO pathway had no effect on blood pressure of MCRT by intracerebroventricular injection.Peripheral NO pathway has nothing to do with the heart rate effect of MCRT,but central NO pathway is involved in regulation on the heart rate of MCRT by central injection,MCRT is one of the the strongest analgesic peptides,which mainly due to it's mixed mu/delta agonist activity;The cardiovascular effects of MCRT,bloodpressure lowering and bradycardiac,is stronger than their parent peptides,opioid receptors and the NO pathway are all involved in the regulation,which have some differences between intravenous and intracerebroventricular.