Compartmental analysis of the efflux of l-[3H]norepinephrine from isolated perfused rat lungs.
Isolated rat lungs, pretreated with 100 microM pargyline and 100 microM U-0521 (3',4'-dihydroxy-2-methylpropriophenone) to block metabolism of norepinephrine (NE), were perfused with 0.3 microM 3H-labeled l-norepinephrine (1-[3H]-NE) for 30 min. Efflux samples were then collected for 30 min during washout of the tissue with amine-free Krebs solution. Compartmental analysis (nonlinear least-squares regression) of the efflux of tissue l-[3H]NE content vs. time indicates that NE is accumulated in a large slowly equilibrating compartment (t 1/2 = 58.15 +/- 6.84 min) in addition to distribution in the vascular (blue dextran tracer) and extracellular ([3H]sorbitol tracer) fluid compartments of the lung. Pretreatment of the lungs with 100 microM cocaine hydrochloride reduces the total l-[3H]NE space from 7.44 +/- 1.91 to 2.48 +/- 0.23 ml/g (P less than 0.05) by selectively decreasing the size of the slow NE compartment from 6.99 +/- 1.97 to 1.67 +/- 0.14 ml/g (P less than 0.05). The large size, cocaine sensitivity, and long efflux half time of this compartment suggest that neuronal uptake contributes to the pulmonary vascular inactivation of l-[3H]NE.
Metting
P J
PJ
Levin
J A
JA
Samuels
J T
JT
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D008722:Methods; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000378:metabolism; D014316:Tritium
D003911:Dextrans; D014316:Tritium; D013012:Sorbitol; C017080:blue dextran; D003042:Cocaine; D009638:Norepinephrine