By CIBA Foundation Symposium

This ebook describes a various research of the 5 somatostatin receptors; somatostatin gene legislation; promatostatin processing; mechanisms of sign transduction; and the layout and use of somatostatin analogues, together with their attainable scientific implications. The publication will offer a complete precis of the mobile and molecular biology of somatostatin and its lately remoted receptors. The publication will evaluation the layout and use of particular somatostatin analogues either biochemically to signify the explicit features of somatostatin and clinically within the therapy of varied tumors.

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For instance, the hypothalamus and cerebral cortex synthesize both somatostatin-14 and somatostatin-28 in an approximate molar ratio of 4:l; whereas the stomach, pancreatic islets, enteric neurons and retina produce almost entirely somatostatin-14 (Patel et a1 1981, 1985). In contrast, intestinal mucosal cells synthesize somatostatin-28 as the principal terminal product. The sequence of somatostatin-14 and prosomatostatin, is conserved between fish and mammals indicating a remarkable structural conservation at both the C- and N-termini of prosomatostatin.

Armstrong, unpublished results). When these cells are stimulated with forskolin, CREB protein activity increases via the same mechanism as in PC12 cells. If these cells are maintained for up to 20 h in forskolin and re-stimulated with forskolin after removing the medium, a peak or similar rise is obtained that is the reverse of cAMP accumulation. Phosphorylation of CREB protein is not observed in response to that stimulation but somatostatin transcription is. We have been able to trace this down to a loss of a catalytic subunit protein.

We have investigated the endogenous and heterologous synthesis and processing of rat prosomatostatin in 1027B2rat islet somatostatinoma cells and in constitutive (COS-7, PC-12) and regulated (AtT-20, GH,/GH,C,) secretory cells. We have correlated processing efficiency with: secretion through the constitutive or regulated pathways; endogenous expression of furin, PCI and PC2; and expression or overexpression of furin, PCI and PC2. Pulse-chase studies showed that prosomatostatin is rapidly and independently processed to somatostatin-I4 and somatostatin-28.

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