Endomorphin-1 and -2 inhibit human vascular sympathetic norepinephrine release: Lack of interaction with μ₃ opiate receptor subtype

AIM: To determine if endomorphin-1 (End-1) and -2 (End-2) interact with μ₃ opiate receptor subtype and in this way cause vascular hypotension. METHODS: Amperometric nitric oxide (NO) determinations associated with opiate binding displacement analysis and preloaded [³H] norepinephrine KCl stimulated release in human vascular tissues from sympathetic nerve fibers in vitro. RESULTS: The endomorphins did not release NO from human monocytes, granulocytes, saphenous vein, and internal thoracic artery endothelium and did not displace opiate alkaloid binding to μ₃ receptor. However, they did inhibit KCl-stimulated [³H]norepinephrine release from vascular nerves. CONCLUSION: The data strongly suggested that End-1 and -2 caused hypotension by blocking sympathetic vascular sympathetic activity.