Delta2 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 the endothelium of human saphenous vein and internal thoracic artery. Displacement analysis revealed that a variety of opioid peptides were found to be ineffective in displacing specifically bound 3H dihydromorphine and only delta2 ligands were effective in regard to 3H Ala2-met5 enkephalinamide (DAMA), indicating the presence of mu3 and delta2 opioid receptor sites, respectively. Confirming the presence of 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, DAMA did not stimulate nitric oxide from either blood vessel and human granulocytes. Additionally, DAMA preadministered before morphine exposure to the endothelium or granulocytes, inhibited the morphine-stimulated release of NO in a dose-dependent manner. The data indicate that opioid peptides and opiate alkaloids regulate endothelial function in an antagonistic manner thereby influencing the microvascular environment.
Stefano
G B
GB
Department of Surgery, Health Sciences Center, State University of New York at Stony Brook, 11794, USA. stefano@surg.som.sunysb.edu
Salzet
M
M
Hughes
T K
TK
Bilfinger
T V
TV
D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009020:Morphine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D012501:Saphenous Vein; D013895:Thoracic Arteries
D017465:Receptors, Opioid, delta; D009569:Nitric Oxide; D004744:Enkephalin, Methionine; D009020:Morphine