Specific binding and clearance of [³H]dynorphin (1–13) in the perfused rat lung: an application of the multiple‐indicator dilution method

Abstract— The clearance and binding of a κ‐selective opioid peptide, dynorphin (1–13), in the perfused rat lung has been examined, using the multiple indicator dilution method. More than 50% of [³H]dynorphin (1–13) entering the pulmonary circulation was eliminated by the lung during a single passage of a tracer dose. By contrast, when a high dose (100 μM) of dynorphin (1–13) was concomitantly injected, [³H]dynorphin (1–13) behaved like [¹⁴C]sucrose, an extracellular marker. The kinetic analyses of the pulmonary venous outflow curves of [³H]dynorphin (1–13) and [¹⁴C]sucrose at low and high doses of dynorphin (1–13) indicated that the initial uptake rate constant, extraction ratio and distribution volume of [³H]dynorphin (1–13) decreased significantly in the presence of a high concentration of unlabelled dynorphin (1–13). These results suggest that [³H]dynorphin (1–13) is eliminated by a saturable process and binds to a specific binding site in the perfused lung, which may be the κ‐type binding site. The multiple indicator dilution technique, in combination with a moment analysis, was successfully applied to demonstrate the specific binding and clearance of dynorphin (1–13) in the perfused lung. 1990 Royal Pharmaceutical Society of Great Britain