Lewis S. Schanker

Phenol red absorption from the rat lung: Evidence of carrier transport

Abstract To investigate the absorption of [ 35 S]phenol red from the rat lung, 0.1 ml of Krebs-Ringer phosphate solution (pH 7.4) containing the compound was administered to anesthetized animals by way of a catheter introduced through a tracheal cannula. After various times, the lungs were removed and assayed for the amount of dye that remained. Studies with 0.01–1 mmol concentrations of phenol red indicated that pulmonary absorption of this anion occurred in part by a saturable, carrier-type transport process and in part by diffusion. Carrier transport became saturated at phenol red concentrations greater than 0.7 mmol, and the transport maximum was estimated to be at least 1.2 μg/ hour. Transport was inhibited by other sulfonic acid dyes and also by benzylpenicillin and cephalothin. The diffusion component of phenol red absorption was in close accord with the rate predicted from the molecular size and diffusion coefficient of the compound. The results indicate that the respiratory tract epithelium, like certain other body membranes, possesses a specialized process for the transport of certain organic anions.

Absorption of Disodium Cromoglycate from the Rat Lung: Evidence of Carrier Transport

1. Pulmonary absorption studies in the rat with 0–01–100 mM solutions of disodium cromoglycate (DSCG) indicated that absorption occurred in part by a saturable, carrier-type transport process and in part by diffusion.2. Carrier transport became saturated at DSCG concentrations greater than 50 mM, and the transport maximum was estimated to be 92 μg/h under the conditions of these experiments.3. Transport was inhibited by certain other organic anions including phenol red, chlorphenol red, benzylpenicillin and cephalothin. Moreover, DSCG inhibited the carrier transport of phenol red.4. The results suggested that DSCG and phenol red share a common transport process for their absorption from the lung.

Diffusion coefficients of some 14C-labeled saccharides of biological interest

Abstract Coefficients of free diffusion of some 14 C-labeled saccharides in saline were determined at 37°C by the agar gel method of Schantz and Lauffer. The following values (× 10 −6 cm 2 /sec) were obtained: [1- 14 C]D-mannitol, 9.16; [U- 14 C]D-sucrose, 6.99; [ 14 C] carboxyinulin, 2.98; [ 14 C] hydroxymethyl-inulin, 2.49; and [ 14 C] carboxydextran (mol wt range 60, 000–90, 000), 1.33. The coefficients for 14 C-labeled mannitol, sucrose, and carboxy-inulin were in reasonably close agreement with previously reported literature values and with Stokes-Einstein calculated coefficients. The value for [ 14 C] hydroxymethyl-inulin differed from that of [ 14 C] carboxy-inulin, but was similar to previously reported values for native (unlabeled) inulin. The measured diffusion coefficient for [ 14 C] carboxydextran was somewhat greater than the coefficient calculated from the Stokes-Einstein equation for a compound with an average molt wt of 75, 000.

Absorption of antibiotics from the rat lung.

Summary Five antibiotics were administered intratracheally as solutions to anesthetized rats. The times necessary for 50% absorption ranged from 1.9 to 33 min. Chloramphenicol was absorbed most rapidly followed by doxycycline, erythromycin, and tetracycline, with benzylpenicillin showing the slowest rate. A comparison of pulmonary absorption rate, molecular weight, and lipoid (chloroform)/water partition coefficient of the drugs indicated that lipoid solubility is more important than molecular size in determining the relative absorption rates. The absorption process for benzylpenicillin, doxycycline, and erythromycin did not become saturated when drug concentrations were raised 10-5000-fold, suggesting that these antibiotics are absorbed mainly by a process of simple diffusion. The authors are indebted to Mrs. Jean C. Henderson for her excellent technical assistance.

Absorption of heparin and cyanocobalamin from the rat lung.

Summary Solutions of heparin and cyanocobalamin were administered through a tight-fitting tracheal cannula into the lungs of anesthetized rats. The times necessary for 50% absorption from the lungs were 3 hr for cyanocobalamin and 9.2 hr for heparin. The absorption process did not become saturated when drug concentrations were raised 100 to 1000-fold, suggesting that both compounds are absorbed mainly by a process of simple diffusion. A comparison of pulmonary absorption rates and diffusion coefficients of heparin and cyanocobalamin with corresponding values reported previously for other lipoid-insoluble compounds indicated that observed absorption rates were close to the rates predicted for the two drugs based on their calculated diffusion coefficients and the view that absorption occurs mainly through membrane pores.

Absorption of Organic Anions from the Rat Small Intestine

Abstract1. Hippuric acid, sulphanilic acid, p-aminohippuric acid, and phenol red, highly ionized compounds of very low lipoid solubilities, were absorbed from the rat small intestine at rates which varied over a 25-fold range.2. Absorption rates ranked in the same order as the chloroform-to-water partition coefficients of the compounds but not in the order of the molecular weights or degrees of ionization.3. The results suggested that these anions are absorbed mainly by simple diffusion through lipoid regions of the intestinal boundary.

Effect of Paraquat-Induced Lung Damage on Permeability of Rat Lung to Drugs

Summary To investigate the effect of paraquat-induced lung damage on pulmonary absorption of drugs, rats were given a single oral dose of paraquat (250 mg/kg), and rates of drug absorption from damaged and control lungs were compared after various times. To measure absorption rates of drugs, 0.1 ml of 10 mM drug solution was administered through a tracheal cannula to anesthetized animals and, after various times, lungs were assayed for unabsorbed compound. Drugs investigated were procaine amide ethobromide, p-aminohippuric acid, and procaine amide. Rates of drug absorption increased 1.4-2.8-fold at 3-5 days after paraquat administration and returned to near control values by the 15th day. The results suggest that paraquat-induced lung damage increases the porosity of the pulmonary epithelium. The authors are indebted to Mrs. Jean C. Henderson for her excellent technical assistance. Appreciation is also extended to Dr. Charles Dunlap and Mrs. Viola Flanagan, Pathology Department, University of Missouri-Kansas City School of Dentistry, Kansas City, Missouri, for the preparation of histologic material.

Effect of carbon tetrachloride-induced liver damage on organic ion transport in rat liver.

The effect of carbon tetrachloride (CCl4) pretretment on the hepatic transport of a cation, procaine amide ethobromide (PAEB), and of an anion, p-acetylaminohippurate (PAAH), was investigated in anesthetized rats with ligated renal pedicles and a cannulated bile duct. Each animal received a single ip injection of CCl4 (1 ml/kg) as a 50% solution in olive oil at times ranging from 0.5 to 71.5 hr prior to an iv injection of PAEB, 5 mg/kg, or PAAH, 20 mg/kg. Control animals were pretreated with olive oil alone. The effect of CCl4 on the biliary excretion rate of PAEB and on the concentration of PAEB in liver 30 min after injection of the cation varied with the time after CCl4 pretreatment. At 1, 2, 4 and 7 hr after CCl4 treatment, the biliary excretion rate of PAEB was depressed, while the concentration of the drug in liver was markedly elevated. The results suggested that the main effect of CCl4 was to decrease the transport of PAEB from liver to bile. In the case of PAAH, there was an increase in the plasma concentration, a decrease in liver concentration, and an even greater decrease in the biliary excretion rate of the compound at all times between 0.5 and 48 hr after CCl4 treatment. The results suggested that the effect of CCl4 treatment was to depress the net transport of PAAH from plasma to liver and also from liver to bile.

Transport and Binding of Chloroguanide-Triazine by Rat Liver Slices

Summary When rat liver slices were incubated aerobically at 37° with 3.5×10-7 M chloroguanide-triazine (CGT), the compound readily entered the tissue against an apparent concentration gradient. After 2 hr, the slice/medium concentration ratio was 9, and after 4 hr about 12. Uptake of CGT into slices occurred by a process that became saturated at high concentrations of the drug. Uptake was diminished by anaerobic conditions and by metabolic inhibitors such as iodoacetate and 2, 4-dinitrophenol. Uptake was also inhibited by certain tertiary and quaternary amine compounds, which pre-iodoacetate and 2, 4-dinitrophenol. Uptake process. These results suggested that CGT is taken up by liver slices at least in part by an active transport process that is closely related to the process which secretes CGT and certain other tertiary and quaternary amines into bile in vivo. CGT also entered liver slices by a process of diffusion. The compound was highly bound to homogenates of rat liver, suggesting that part of the accumulation seen in liver slices results from binding to tissue components.

Effect of Papain-Induced Emphysema on Permeability of Rat Lung to Drugs

Summary To investigate the effect of a papain-induced emphysema-like condition on pulmonary absorption of drugs, rats were exposed to either papain aerosol or distilled water aerosol (control) intermittently for 2 wk, and rates of drug absorption from damaged and control lungs were compared. To measure absorption rates, 0.1 ml of drug solution (0.1-10 mM) was administered through a tracheal cannula to anesthetized animals, and after various times lungs were assayed for unabsorbed compound. In absorption experiments with the lipoid-insoluble compounds, mannitol, p-aminohippuric acid, and procaine amide ethobromide, all three drugs were absorbed from the lungs about twice as rapidly in papain-treated rats as in control. In contrast, procaine amide, a relatively lipoid-soluble drug, was absorbed at the same rate in both control and papain-treated animals. The results suggest that papain-induced lung damage increases the porosity of the pulmonary epithelium. The authors are indebted to Mrs. Jean C. Henderson for her excellent technical assistance. Appreciation is also extended to Dr. Charles Dunlap and Mrs. Viola Flanagan, Pathology Dept., University of Missouri-Kansas City School of Dentistry, Kansas City, Missouri, for the preparation of histologic material.