In Parkinson's disease (PD), dopaminergic input to the caudate nucleus and a band of putaminal tissue abutting the external globus pallidus seems well preserved on immunohistochemical staining for the dopamine transporter. Counting of dopaminergic terminals showed that terminal density in these regions in PD was the same as that in controls, which indicates that input is truly preserved and not a consequence of a compensatory upregulation of metabolism in a reduced pool of surviving terminals. When the branching pattern of dopaminergic axons coursing through the globus pallidus was examined, we found no evidence for increased axonal sprouting in PD that might have contributed to preservation of dopaminergic input to the putamen or caudate nucleus. Although terminal counting indicated that anatomic input was preserved to parts of the striatum, dopamine uptake site density in these regions was reduced significantly. This suggests that the impact of disease in these areas is more profound than was thought previously.

The structural relationships among the gag polyproteins Pr655"9, Pr75 a8, and gPr80959 of Rauscher murine leukemia virus were studied by endoglycosidase H digestion and formic acid cleavage. Fragments were identified by precipitation with specific antisera to constituent virion structural proteins followed by onedimensional mapping. Endoglycosidase H reduced the size of gPr80959 to that of Pr759'a. By comparing fragments of gPr80g'w and the apoprotein Pr759'9, the former was shown to contain two mannose-rich oligosaccharide units. By comparing fragments of Pr65""9 and Pr755 ¶9, the latter was shown to differ from Pr659"9 at the amino terminus by the presence of a leader peptide approximately 7,000 daltons in size. The internal and carboxyl-terminal peptides of the two unglycosylated polyproteins were not detectably different. The location of the two N-linked carbohydrate chains in gPr80"g" has been specified. One occurs in the carboxyl-terminal half of the polyprotein at asparagine,77 of the p30 sequence and the other is found in a 23,000-dalton fragment located in the amino-terminal region of gPr809a9 and containing the additional amino acid sequences not found in Pr65gag plus a substantial portion of p15. MATERIALS AND METHODS Cells and cell culture. JLS-V9 cells (36) chronically infected with R-MuLV were obtained from the Viral Resources Laboratory (Frederick Cancer Research Center, Frederick, Md.). Fetal calf serum was purchased from GIBCO Laboratories (Grand Island, N.Y.). Eagle minimal essential medium (EMEM) and methionine-free EMEM were obtained from Flow Laboratories (Rockville, Md.). Cells were grown on Corning plastic ware in EMEM supplemented with 10% heat-inactivated fetal calf serum, penicillin (100 IU/ml), and streptomycin (100 ,ug/ 581

Amidated and nonamidated progastrin-derived peptides have distinct biological activities that are mediated by a range of receptor subtypes. The objective was to determine the nature of the stored and secreted progastrin-derived peptides and to investigate whether progastrin release is regulated by gastric acidity. Using an antiserum directed to the C terminus of progastrin for identification and to monitor purification, C-terminal flanking peptides (CTFP) of progastrin (prog(76-83), prog(77-83), and prog(78-83) in approximately equivalent amounts) were isolated and identified from extracts of sheep antrum using ion exchange, HPLC, and mass spectrometry. Only trace amounts of full-length progastrin were present. Progastrin CTFP was the predominant progastrin-derived peptide in the antrum [progastrin CTFP/gastrin amide (Gamide) = 3]. Similarly, progastrin CTFP was the major circulating form in the antral (CTFP, 710 +/- 62 pmol/liter; Gamide, 211 +/- 35 pmol/liter) and jugular (CTFP, 308 +/- 16 pmol/liter; gastrin amide, 32 +/- 3 pmol/liter) veins. Alteration of gastric acidity in sheep by iv infusion of a H/K-adenosine triphosphatase inhibitor or somatostatin or by intragastric infusion of HCl demonstrated that the CTFP concentrations changed, although to a lesser extent than the changes in circulating gastrin amide. We conclude that the CTFP of progastrin is the major stored and circulating species of the gastrin gene, and that it is secreted in a regulated fashion rather than constitutively. Because full-length progastrin is bioactive, but is only a minor antral and secreted form, determination of the biological activity of the C-terminal flanking peptides will be important for a complete understanding of gastrin endocrinology.