Lars-Erik Appelgren

The uptake and distribution of [3H]benzo[a]pyrene in the Northern pike (Esox lucius). Examination by whole-body autoradiography and scintillation counting.

The uptake and distribution of the polyaromatic hydrocarbon benzo[a]pyrene in Northern pike (Esox lucius) were investigated by whole body autoradiography and scintillation counting. [3H]Benzo[a]pyrene was administered either in the diet or in the water. The levels of this xenobiotic employed corresponded to levels found in moderately polluted water. The uptake and distribution of this compound and its metabolites were followed from 10 hr to 21 days after the initial exposure. The autoradiography patterns observed here with both routes of administration suggest, as expected, that benzo[a]pyrene is taken up through the gastrointestinal system and the gills, metabolized in the liver, and excreted in the urine and bile. Other findings indicate that the gills may not be a major route of excretion for benzo[a]pyrene and its metabolites in the Northern pike; that benzo[a]pyrene may be taken up from the water directly into the skin of this fish; that benzo[a]pyrene and its metabolites are heterogeneously distributed in the kidney of the Northern pike; and that very little radioactivity accumulates in the adipose tissue. With scintillation counting, uptake of radioactivity from the water was found to occur rapidly in all organs, reaching a plateau in most cases after about 0.8 days. The concentrations of radioactivity in different organs ranged between 50 (many organs) and 80,000 (gallbladder + bile) times that found in the surrounding water. Since most of the radioactivity recovered in different organs of the pike after 8.5 days of exposure was in the form of metabolites, we feel that metabolism may play an important role in the bioconcentration of xenobiotics in fish.

The distribution of a potential Molluscicide, 3H‐aridanin, in mice (Mus Musculus) and snails (Biomphalaria Glabrata)

The molluscicide Aridanin was labelled with 3H and its tissue distribution was studied in mice and snails (B. glabrata) by whole‐body autoradiography and liquid scintillation. In mice intravenously injected 3H‐Aridanin was rapidly taken up in the kidney and liver. Its elimination—mainly through the faeces and to a lesser extent through the urine—was rapid. About 40 % of the total Aridanin dose was excreted after 24 h. No specific retention in any tissue was observed after 24 h and Aridanin did not pass the placental barrier in pregnant mice. After oral administration to mice most of the labelled Aridanin was found in the intestinal contents indicating a very poor absorption. In the snails incubated in labelled Aridanin the radioactivity was extensively concentrated in comparison to the surrounding medium, and a retention was registered in many organs (kidneys, hepatopancreas, gastrointestinal tract) up to 72–96 h after incubation. A gradual increase in the ovotestes was observed during the experiment. Pre...

Melanin affinity: a possible explanation of isoxsuprine retention in the horse

Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H-isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The K(d) values were 0.02 mmol/l and 1 mmol/l, and the B(max) values were 0.2 micromol/mg and 2 micromol/mg, respectively. A low affinity site with approximately the same K(d) and B(max) as keratin was also detected for melanin. 3H-isoxsuprine was found to have affinity to pigmented horse skin after incubation in vitro and microautoradiography. We believe that affinity to melanin and possibly also to keratin can cause retention of the drug in the body and therefore explain the prolonged excretion of low levels of isoxsuprine in the horse.

Muscarinic receptors in equine airways.

The distribution of muscarinic receptors in equine airways was investigated using autoradiography. Frozen sections of tissue from six different levels in the bronchial tree, from the trachea to the distal bronchioles, were incubated in vitro with 1.5 nmol/L of the muscarinic receptor antagonist 1-[N-methyl-3H]scopolamine methyl chloride (3H-NMS). In addition, the subtype pattern of muscarinic receptors was investigated in equine tracheal smooth muscle using radioligand binding with methoctramine, tripinamide, 4-DAMP-methiodide and pirenzipine as competitors against the binding of 1.3 nmol/L 3H-NMS. The autoradiograms showed specific labelling indicating a high density of muscarinic receptors in smooth-muscle tissue in all levels of the airway tree investigated. Besides muscle tissue, subepithelial glands were the only structures specifically labelled. The dominating subtypes in tracheal smooth muscle investigated with radioligand binding studies were found to be M2 and M4, as both methoctramine (pKd = 8.5) and tripinamide (pKd = 8.6 and 6.7 for two different sites) showed high affinity. The density of the M3-muscarinic receptor subtype was low, but this subtype could be detected with statistical significance when methoctramine was used as the competitor against 3H-NMS binding.