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Journal of Pharmacology And Experimental Therapeutics, Vol. 186, Issue 3, 498-507, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

HYPOTHERMIC INHIBITION OF 5-HYDROXYTRYPTAMINE AND NOREPINEPHRINE UPTAKE BY LUNG: CELLULAR LOCATION OF AMINES AFTER UPTAKE

Y. IWASAWA 1, C. N. GILLIS 1, and G. AGHAJANIAN 1

1 Department of Anesthesioloqy, Pharmacology and Psychiatry, Yale University School of Medicine, New Haven, Connecticut

The effect of hypothermia (6°C) on removal of 5-hydroxytryptarmine (5-HT) and norepinephrine (NE) by rabbit lung was studied with a technique that permits use of simultaneously but independently perfused left and right lungs as paired organs. At 35°C, removal of both amines obeyed saturation kinetics. Apparent Km and Vmax for both 5-HT (5.2 µM and 12.8 mµmol/g/min, respectively) and NE (2.4 µM and 5.7 mµmol/g/min, respectively) removal were similar to those reported previously for rat lung. Perfusioin at 6°C reversibly inhibited 5-HT and NE (1.5 µM) removal. The Q10 (25-35°C) for temperature-sensitive uptake of 5-HT was 2.0, while that for NE was 2.4. Removal of both amines was significantly (P < .01) reduced by ouabain (10-4 M) and by iodoacetate (10-4 M) but was only minimally lowered by anoxia and was unaffected by omission of glucose. In lungs perfused with amines at 35°C. specific NE and 5-HT fluorescence was seen only in adrenergic nerve endings of large arteries and larger arterioles. After similar amine perfusion in the presence of pargyline and/or tropolone, intense fluorescence was also found in the endothelium of capillaries and postcapillary venules. Perfusion of amines at 6°C (in the presence of pargyline and/or tropolone) conmpletely abolished endothelial fluorescence; mast cell fluorescence was unaffected by hypothermia. Accordingly. 5-HT and NE uptake processes are saturable, temperaturesensitive and linked to a sodium, potassium adenosine triphosphatase. Energy for uptake may be supplied by noncarbohydrate substrates. The site for uptake and metabolism of both amines is likely to be endothelium of capillaries and small venules.

Submitted on January 15, 1973
Accepted on April 25, 1973




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Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics.