Stereospecific opiate binding in living human polymorphonuclear leucocytes

Area of Science:

• Immunology
• Pharmacology
• Cell Biology

Background:

• Polymorphonuclear leukocytes (PMNs) are key immune cells.
• Opiate receptors are known to exist in the central nervous system.
• The presence and function of opiate receptors on immune cells are less understood.

Purpose of the Study:

• To investigate the binding of various opiate agonists and antagonists to living human polymorphonuclear leukocytes.
• To characterize the nature and location of potential opiate binding sites on these immune cells.

Main Methods:

• Radioreceptor assays were performed using radiolabeled opiate ligands.
• Incubation of human PMNs with ligands was conducted at different temperatures (4°C and 37°C).
• Autoradiography was used to visualize the cellular localization of ligand binding.

Main Results:

• Opiate antagonists (3H-naloxone, 3H-diprenorphine) and a benzomorphan (3H-ethylketocyclazocine) showed binding at both temperatures.
• 3H-naloxone binding demonstrated stereospecificity at 37°C.
• An opiate agonist (3H-dihydromorphine) bound at 37°C but not at 4°C, with a distinct time course.
• No specific binding was observed for a stable enkephalin analogue (3H-D-Ala-D-Leu-enkephalin).
• Autoradiography revealed non-specific intracellular accumulation of 3H-naloxone and specific binding at the cell membrane.

Conclusions:

• Human polymorphonuclear leukocytes possess specific opiate binding sites, primarily located at the cell membrane.
• These findings suggest a potential role for immunomodulation through opiate receptor interactions on immune cells.
• The differential binding of agonists and antagonists may indicate distinct receptor subtypes or conformational states on PMNs.