Abstract
[Phe4]Somatostatin was twice as active as somatostatin (SS) in suppressing rat growth hormone release in vitro but had only weak activity toward inhibition of insulin and glucagon release in vivo. The ability of this analogue to inhibit growth hormone release more actively than SS was confirmed in vivo by two separately designed bioassays. Further structure/activity studies of position 4 were carried out with [Glu4]SS, [Thr4]SS, and des-Lys4-SS, all of which had negligible inhibiting activity in the pituitary and pancreas. In this context the strikingly selective activity of [Phe4]SS suggests a fundamental difference in the SS receptors of pituitary and pancreas and the normal side-chain basicity of position 4 appears to be more important for action in pancreas than in pituitary. [Phe4]SS has properties that may be useful in the development of agents for the treatment of acromegaly or other disorders associated with increased growth hormone levels.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Birge C. A., Peake G. T., Mariz I. K., Daughaday W. H. Radioimmunoassayable growth hormone in the rat pituitary gland: effects of age, sex and hormonal state. Endocrinology. 1967 Aug;81(2):195–204. doi: 10.1210/endo-81-2-195. [DOI] [PubMed] [Google Scholar]
- Coy D. H., Coy E. J., Arimura A., Schally A. V. Solid phase synthesis of growth hormone-release inhibiting factor. Biochem Biophys Res Commun. 1973 Oct 15;54(4):1267–1273. doi: 10.1016/0006-291x(73)91124-8. [DOI] [PubMed] [Google Scholar]
- Garsky V. M., Clark D. E., Grant N. H. Synthesis of a nonreducible cyclic analog of somatostatin having only growth hormone release inhibiting activity. Biochem Biophys Res Commun. 1976 Dec 20;73(4):911–916. doi: 10.1016/0006-291x(76)90208-4. [DOI] [PubMed] [Google Scholar]
- Gordin A., Meyers C., Arimura A., Coy D. H., Schally A. V. An in vivo model for testing inhibition of arginine-induced insulin and glucagon release by somatostatin analogs. Acta Endocrinol (Copenh) 1977 Dec;86(4):833–841. doi: 10.1530/acta.0.0860833. [DOI] [PubMed] [Google Scholar]
- Grant N., Clark D., Garsky V., Jaunakais I., McGregor W., Sarantakis D. Dissociation of somatostatin effects. Peptides inhibiting the release of growth hormone but not glucagon or insulin in rats. Life Sci. 1976 Sep 1;19(5):629–631. doi: 10.1016/0024-3205(76)90158-2. [DOI] [PubMed] [Google Scholar]
- Meyers C. A., Coy D. H., Huang W. Y., Schally A. V., Redding T. W. Highly active position eight analogues of somatostatin and separation of peptide diastereomers by partition chromatography. Biochemistry. 1978 Jun 13;17(12):2326–2331. doi: 10.1021/bi00605a011. [DOI] [PubMed] [Google Scholar]
- Meyers C., Arimura A., Gordin A., Fernandez-Durango R., Coy D. H., Schally A. V., Drouin J., Ferland L., Beaulieu M., Labrie F. Somatostatin analogs which inhibit glucagon and growth hormone more than insulin release. Biochem Biophys Res Commun. 1977 Jan 24;74(2):630–636. doi: 10.1016/0006-291x(77)90349-7. [DOI] [PubMed] [Google Scholar]
- Sarantakis D., Teichman J., Clark D. E., Lien E. L. A bicyclo-somatostatin analog, highly specific for the inhibition of growth hormone release. Biochem Biophys Res Commun. 1977 Mar 7;75(1):143–148. doi: 10.1016/0006-291x(77)91301-8. [DOI] [PubMed] [Google Scholar]
- Vale W., Grant G., Amoss M., Blackwell R., Guillemin R. Culture of enzymatically dispersed pituitary cells: functional validation of a method. Endocrinology. 1972 Aug;91(2):562–572. doi: 10.1210/endo-91-2-562. [DOI] [PubMed] [Google Scholar]