Inhibition by K+ of uptake2 of 3H-(+/-)-isoprenaline in the perfused rat heart.
The kinetics of the inhibitory effect of extracellular K+ on uptake2 of 3H-(+/-)-isoprenaline were determined in isolated hearts obtained from reserpine-pretreated rats; catechol-O-methyl transferase was inhibited. Initial rates of uptake2 of a very low concentration of 3H-(+/-)-isoprenaline (10 nmol/l) were determined in the presence of various extracellular concentrations of K+ (2.7 to 60 mmol/l). The inhibitory effect of K+ was concentration-dependent with an IC50 of about 20 mmol/l. - In these experiments KCl was added to the perfusion solution, and some hypertonicity resulted. In some experiments NaCl was added to a solution containing 5 mmol/l K+ to result in the same degree of hypertonicity as that obtained for 60 mmol/l K+; hypertonicity increased the initial rate of uptake2 of 3H-(+/-)-isoprenaline. Thus, the inhibitory effect of K+ had been slightly underestimated. In subsequent experiments the increase of the concentration of K+ in the perfusion fluid to 30 mmol/l was compensated for by a corresponding reduction of Na+. Initial rates of uptake2 of 10 nmol/l 3H-(+/-)-isoprenaline were determined in the absence and presence of various concentrations of unlabelled (+/-)-isoprenaline. At 30 mmol/l K+ the IC50 (= Km for uptake2) did not significantly differ from that determined in an earlier study at 2.7 mmol/l K+ (Grohmann and Trendelenburg 1984). Finally, the Vmax for uptake2 of 3H-(+/-)-isoprenaline was determined at either 2.7 or 30 mmol/l K+. At 30 mmol/l K+ the Vmax was only about 1/4 of that observed at 2.7 mmol/l K+.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011189:Potassium Chloride; D007545:Isoproterenol; D011188:Potassium