The melanin affinity of manganese was studied in vitro using melanin isolated from beef eyes or human hair, and synthetic dopamine melanin, which is known to be structurally similar to the melanin present in the pigmented nerve cells in the human substantia nigra. In addition, the uptake of manganese in melanin containing tissues in vitro and in vivo was studied by whole body autoradiography. Manganese was bound to beef eye, human hair and synthetic dopamine melanin, and was taken up in pigmented tissues in mice and a monkey. Long-time exposure to manganese may cause a chronic extrapyramidal disorder. It is suggested that manganese, due to its neurotoxicity, may cause lesions in pigment containing neurones in the substantia nigra secondary to its accumulation on the neuromelanin.

A recently discovered neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, has been found to cause a parkinsonian-like syndrome in man and monkey, but not in laboratory animals such as rat, mouse and guinea pig. MPTP seems to selectively destroy the melanin containing dopaminergic cells in pars compacta of substantia nigra. Lower mammalian species do not have melanin in these cells, which indicates that the presence of neuromelanin may be of importance for the development of MPTP-induced lesions. By means of whole-body autoradiography of 3H-MPTP in mice, accumulation and retention was observed in the dopaminergic pathways, in locus caeruleus and in structures in the medulla oblongata and spinal cord. A high uptake was also seen in melanin-containing tissues such as in the eyes of pigmented mice. MPTP has earlier been found to have high affinity in vitro for dopamine melanin, which is similar to the pigment in substantia nigra. The typical features of the MPTP-induced neurotoxicity with destruction of pigmented nerve cells and development of parkinsonism may be to to accumulation and retention of MPTP and its metabolites in these cells. In species with pigmented nerve cells, such as man and monkey, the accumulation may be much more pronounced because of the melanin affinity of MPTP and its metabolites.

The characteristics of interaction of insulin with specific receptors on exocrine pancreatic cells of the guinea pig have been studied. Insulins from different species as well as certain insulin analogs were found to have affinities to receptors on pancreatic acinar cells which are similar to what have been described for insulin receptors in other organs of different mammalian species. Binding was rapid and reversible at 37 C but dissociation was markedly slower at 12 C. Clear indications of negative cooperativity between binding sites were not seen. Bovine and chicken insulin bound with approximately a 100-fold higher affinity to guinea pig insulin receptors than guinea pig insulin itself. The number of insulin receptors per acinar cell were comparable with what has been described for other mammalian cells. Part of cell-associated insulin was internalized. After 60 min of incubation the major part of radioactivity in the incubation medium as well as in cells appeared as intact [125I] iodoinsulin on a Sephadex G-50 column and less than 12% of radioactivity was eluted as breakdown products together with Na 125I.

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By means of whole‐body autoradiography, the general distribution of 54MnCl2 was studied in mice and a Marmoset monkey. High accumulation and retention were observed in the pancreas in both species. Gamma counting experiments in mice after a single intravenous injection of 54MnCl2 showed that the level in the pancreas exceeded that of the liver at all survival times (20 min. — 30 days). Also in the monkey, the concentration in the pancreas exceeded that of the liver, and the pancreas had the highest tissue/liver ratio of the organs measured at 24 hours after injection. The high uptake and long retention in the pancreas suggest that manganese is of importance for the pancreatic function but also that the pancreas may be a target organ for manganese toxicity. Positron tomography, using 11C‐labelled amino acids, has been found to be a promising diagnostic technique for the study of pancreatic disease. Positron emitting manganese isotopes may be worth further studies as possible agents for pancreatic imaging.