The Mechanism Of The Vasodepressor Activity Induced By Endomorphin-1, A Preliminary Experimental Study

Endomorphin-1(EM-1, Tyr-Pro-Trp-Phe-NH2) and endomorphin-2(EM-2,Tyr-Pro-Phe-Phe-NH2) were first isolated and identified in bovine brain and human cortexby Zadina’s group in1997. They bound to the μ-opioid receptor with high affinity andselectivity (EM-1, Ki=0.36nmol/L, σ/μ=4000, κ/μ=15000; EM-2, Ki=0.39nmol/L,σ/μ=13000, κ/μ=15000), and thus were proposed as specific endogenous ligands forμ-opioid receptor（MOR）.For their potent biological activity, both tetrapeptides have been extensively studied,most among which were about their involvement in pain modulation. Their effects oncardiovascular system have just been recognized recently. Champion’s team found thatthrough intravenous injection, both endomorphins had vasodepressor activity and candecrease blood pressure in the rat, mouse and rabbit. In vitro study confirmed that bothtetrapeptides induced vasorelaxant responses in isolated rat and rabbit aorta. Kastin’s workdemonstrated the existence of an efflux system across the blood-brain barrier which cansaturably transport endomorphins across blood-brain-barrier from brain to blood. However,the mechanism of their vasodepressor activity and the distribution of μ-opioid receptor in the cardiovascular system remained unclear.This study was composed by2parts:1. We hypothesized that peripheral endomorphin levels may change in hypertensionpatients. Blood samples from36primary hypertension patients and32healthy volunteerswere analyzed by radioimmunoassay.2. We tried to figure out the distribution of μ opioid receptor in the thoracic aorta,heart and kidney of the rat. An immunohistochemistry (IHC) technique was used to detectμ opioid receptor in the frozen sections of the cardiovascular system and kidney tissue of10normal Sprague-Dawley rats.The main results of this study were as follow:1. Primary hypertension patients had lower blood endomorphin-1levels (838±91pg/ml vs1157±84pg/ml, P<0.01) compared with healthy volunteers.2. Multi correlation analysis showed peripheral endomorphin-1level was related withage.3. The immunoreactivity（IR）of the μ opioid receptor was localized in themembrane of endothelial cells of aorta and the capillaries of the glomerulus. No MORimmunoreactivity was detected in the heart.The conclusions of this study were as the followings:1. Peripheral endomorphin-1levels were lower in primary hypertension patients thanin healthy volunteers.2. Peripheral endomorphin-1levels were related with age.3. Peripheral μ opioid receptors may take part in the vasodepressor responses inducedby endomorphin-1.