CIBA Foundation Symposium's Ciba Foundation Symposium 190 - Somatostatin and its PDF

By CIBA Foundation Symposium

ISBN-10: 0470514736

ISBN-13: 9780470514733

ISBN-10: 0471953822

ISBN-13: 9780471953821

This ebook describes a various research of the 5 somatostatin receptors; somatostatin gene rules; promatostatin processing; mechanisms of sign transduction; and the layout and use of somatostatin analogues, together with their attainable medical implications. The publication will supply a accomplished precis of the mobile and molecular biology of somatostatin and its lately remoted receptors. The ebook will assessment the layout and use of particular somatostatin analogues either biochemically to signify the explicit capabilities of somatostatin and clinically within the remedy of assorted tumors.


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Extra resources for Ciba Foundation Symposium 190 - Somatostatin and its Receptors

Sample text

It has a C-terminal cysteine that is, on the basis of sequence comparison with homologous endoproteases, a putative component of the catalytic reaction. 61). We reported the sequence of the latter enzyme recently (Pierotti et a1 1994). Rat, human and Drosophilu insulin-degrading enzymes belong to the pitrilysin family. 44). The amino acid sequence of protease I11 is 45% homologous to that of the NRD convertase. The NRD convertase is the endoproteolytic component of the so-called somatostatin convertase and contains the Asp/Glu-rich region.

To determine the role of furin in monobasic prosomatostatin processing, we compared the heterologous processing of rat prosomatostatin in COS-7 cells overexpressing human furin using vaccinia furin infection experiments. 4 pfdcell) and then transfected with the plasmid pMJ 601 :rPSS. After 20 h, cells were incubated for 4 h in secretion media, then cells and media were collected for HPLC analysis of somatostatin-14, somatostatin-28 and unprocessed prosomatostatin. Expression of human furin was confirmed by Northern blots hybridized with the rat furin probe and showed only endogenous furin mRNA in control cells whereas W:hfurin infected cells expressed dose-dependent amounts of a second 3 kb mRNA transcript corresponding to human furin mRNA.

In contrast to COS-7 and PC-12 cells, AtT-20 cells not only targeted prosomatostatin-derived peptides to the regulated secretory pathway but also processed prosomatostatin efficiently to both somatostatin-14 and somatostatin-28 (85% and 12% of total somatostatin-14-11 respectively in cell 32 Patel & Galanopoulou extracts) (Fig. 2). Unprocessed prosomatostatin represented only 3 % of total cellular somatostatin-14-11. GH3 cells synthesized and stored somatostatin-14-LI and responded to secretagogues with stimulated release.

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