DELTA(2) OPIOID RECEPTOR SUBTYPE ON HUMAN VASCULAR ENDOTHELIUM UNCOUPLES MORPHINE STIMULATED NITRIC-OXIDE RELEASE

We demonstrate the presence of both delta and mu opioid receptors on t he endothelium of human saphenous vein and internal thoracic artery. D isplacement analysis revealed that a variety of opioid peptides were f ound to be ineffective in displacing specifically bound H-3 dihydromor phine and only delta(2) ligands were effective in regard to H-3 Ala(2) -met(5) enkephalinamide (DAMA), indicating the presence of mu(3) and d elta(2) opioid receptor sites, respectively. Confirming the presence o f both mu and delta sites we demonstrated positive immunostaining with anti-delta and anti-mu receptor antibodies. Exposure of these vessels to DAMA significantly enhances granulocyte adherence (P<0.01) even in vessels 5 min later exposed to 10(-6) M morphine. Unlike morphine, DA MA did not stimulate nitric oxide from either blood vessel and human g ranulocytes. Additionally, DAMA preadministered before morphine exposu re to the endothelium or granulocytes, inhibited the morphine-stimulat ed release of NO in a dose-dependent manner. The data indicate that op ioid peptides and opiate alkaloids regulate endothelial function in an antagonistic manner thereby influencing the microvascular environment . (C) 1998 Elsevier Science ireland Ltd.