Faculty Bibliography

The present study describes the inhibition of [3H]SCH-23390 binding to striatal dopamine D1 receptors in the presence of ascorbic acid. Specific [3H]SCH-23390 binding was maximally inhibited by 0.1 mM ascorbic acid. As determined by Scatchard analysis the binding in the presence of 0.01, 0.1, or 10 mM ascorbic acid was consonant with non-competitive inhibition with a 26%, 38%, or 19% decrease, respectively, in the maximal number of binding sites; the affinity of these binding sites was not affected. Inhibition of [3H]SCH-23390 binding by ascorbic acid was reversible; striatal homogenates incubated with 0.1 mM ascorbic acid and subsequently washed free of ascorbic acid had the same Scatchard parameters as untreated preparations

We examined the regional distribution in rat brain of calpain II, the calcium-activated neutral proteinase maximally active in the presence of 2mM Ca(2+), and of calpastatin, the endogenous inhibitor of the enzyme. A single-step chromatographic procedure was used to separate the constituents before determination. With [methyl-(14)C]?-casein as substrate, specific activity of calpain II was lowest in the cortex. The activity in the other areas tested was 10-50% higher, except pons-medulla > spinal cord > cerebellum > hypothalamus > striatum > hippocampus > cortex. When calpain II activity of the various areas was tested with endogenous brain protein substrates (the neurofilament proteins NF 200, 150 and 70 [NFT], glial fibrillary acidic protein [GFAP], desmin and actin), activity in each substrate was seen to be heterogenous, with a slightly different pattern of heterogeneity for each. The pons-medulla again was the highest in activity, but the cortex was usually not the lowest. Calpastatin was somewhat more evenly distributed in the various brain regions examined. Comparison of the enzyme activity of the crude supernatant with that in the purified fraction showed that at least 50% of the activity in the supernatant was inhibited by the calpastatin present. The regional differences in the substrate specificity of neutral proteolytic activity indicate that in vivo protein metabolism is influenced regionally by heterogeneity both in enzyme and in substrate distribution

This issue of the journal honors Professor Henry McIlwain for his contributions to our knowledge of neurochemistry, as a pioneer (an important contributor already in the 1950s), as a scientist, and as a teacher of great influence and help to the next generation of neurochemists. It is fitting that in his semi-retirement he turns his interest to the history and background of our discipline and demonstrates to us that there is a great deal to learn from the past. In today's explosion of knowledge and new approaches, and the consequent rush to do the work, we tend to forget not only the important past accomplishments but also the past mistakes not to be repeated. It is worthwhile from time to time to take stock, to look back at the path that led to the present. This paper is an attempt to explore this retrospection by a discussion of some of the background of research on cerebral amino acid transport. Emphasis for the purpose is on illustration, with arbitrarily selected examples rather than an exhaustive review of the subject