Specific binding and clearance of [3H]dynorphin (1-13) in the perfused rat lung: an application of the multiple-indicator dilution method.
The clearance and binding of a kappa-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 microM) 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 kappa-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.
Sato
H
H
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Terasaki
T
T
Tsuji
A
A
D000700:Analgesics / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D004399:Dynorphins / Q000378:metabolism / Q000493:pharmacokinetics*; D007201:Indicator Dilution Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism / Q000493:pharmacokinetics
D000700:Analgesics; D010446:Peptide Fragments; D013395:Sucrose; C026843:dynorphin (1-13); D004399:Dynorphins