This Article Full Text Full Text (PDF) All Versions of this Article: 149/4/1600    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rehfeld, J. F. Articles by Friis-Hansen, L. Search for Related Content PubMed PubMed Citation Articles by Rehfeld, J. F. Articles by Friis-Hansen, L.

The Cell-Specific Pattern of Cholecystokinin Peptides in Endocrine Cells Versus Neurons Is Governed by the Expression of Prohormone Convertases 1/3, 2, and 5/6

Department of Clinical Biochemistry (J.F.R., J.R.B., J.H., L.F.-H.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and Department of Biochemistry and Molecular Biology (X.Z., C.N., D.F.S.), University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: J. F. Rehfeld, Department of Clinical Biochemistry (KB 3014), Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: jens.f.rehfeld{at}rh.regionh.dk.

Most peptide hormone genes are, in addition to endocrine cells, also expressed in neurons. The peptide hormone cholecystokinin (CCK) is expressed in different molecular forms in cerebral neurons and intestinal endocrine cells. To understand this difference, we examined the roles of the neuroendocrine prohormone convertases (PC) 1/3, PC2, and PC5/6 by measurement of proCCK, processing intermediates and bioactive, -amidated, and O-sulfated CCK peptides in cerebral and jejunal extracts of null mice, controls, and in the PC5/6-expressing SK-N-MC cell-line. In PC1/3 null mice, the synthesis of bioactive CCK peptide in the gut was reduced to 3% of the translational product, all of which was in the form of -amidated and tyrosine O-sulfated CCK-22, whereas the neuronal synthesis in the brain was largely unaffected. This is opposite to the PC2 null mice in which only the cerebral synthesis was affected. SK-N-MC cells, which express neither PC1/3 nor PC2, synthesized alone the processing intermediate, glycine-extended CCK-22. Immunocytochemistry confirmed that intestinal endocrine CCK cells in wild-type mice express PC1/3 but not PC2. In contrast, cerebral CCK neurons contain PC2 and only little, if any, PC1/3. Taken together, the data indicate that PC1/3 governs the endocrine and PC2 the neuronal processing of proCCK, whereas PC5/6 contributes only to a modest endocrine synthesis of CCK-22. The results suggest that the different peptide patterns in the brain and the gut are due to different expression of PCs.