Renal handling and effects of [3H]digoxin and interactions with quinidine in the avian kidney.
Renal handling and effects of tritium digoxin and interactions with quinidine in the avian kidney were studied using a modified Sperber technique. Results showed that tritium digoxin was extracted at the peritubular side of the nephron in a process competitively inhibited by increasing amounts of unlabelled digoxin. Light microscope autoradiography showed distinct concentrations of silver grains only over distal tubules in the injected kidney. Inhibition of the proximal tubular transport systems for organic anions and cations, respectively, did not change extraction. Addition of quinidine to the injection solution up to an estimated concentration of 1.4 X 10(-5) M in systemic blood significantly lowered 1 min peritubular extraction of tritium digoxin. However, when the amount of quinidine was further increased, extraction of tritium digoxin augmented significantly. Tritium recovery in urine after renal portal bolus injection of tritiated and unlabelled digoxin already showed a distinct ipsilateral peak 2 min after injection with an equally distinct peak of ipsilateral sodium excretion appearing 1 min later. When quinidine was added to the bolus ipsilateral tritium recovery in urine (0-7 min) was halved, with the true tubular excretion fraction (TTEF) lowered by two-thirds, but without changes in the magnitude of ipsilateral natriuresis. Contralateral natriuresis increased more than four-fold with quinidine in the bolus in spite of unchanged tritium recovery in the urine. Thus, our results show tritium digoxin to be extracted from peritubular blood through a specific process probably localized to the distal nephron of the avian kidney.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001345:Autoradiography; D001693:Biological Transport, Active / Q000187:drug effects; D004077:Digoxin / Q000008:administration & dosage / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D007444:Inulin / Q000008:administration & dosage; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D009318:Natriuresis / Q000187:drug effects; D011200:Poultry; D011802:Quinidine / Q000008:administration & dosage / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D004077:Digoxin; D007444:Inulin; D000254:Sodium-Potassium-Exchanging ATPase; D011802:Quinidine