Rapid Identification of Subtype-Selective Agonists of the Somatostatin Receptor Through Combinatorial Chemistry
| Autor: | Steven M. Hutchins, James M. Schaeffer, Lihu Yang, Wanda W.-S. Chan, Ralph T. Mosley, Alex Pasternak, Min Shu, Sylvia J. Degrado, Scott C. Berk, Forrest Foor, Roy G. Smith, John M. Klopp, Sudha W. Mitra, Arthur A. Patchett, Sheng-Jian Cai, Kevin T. Chapman, Yusheng Xiong, Rupa M. Parmar, Dong-Ming Shen, Allan D. Blake, Elizabeth T. Birzin, Susan P. Rohrer, Edward C. Hayes |
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| Rok vydání: | 1998 |
| Předmět: |
endocrine system
medicine.medical_specialty Molecular Sequence Data Pharmacology Biology Ligands Somatostatin Receptor Agonist Cell Line Islets of Langerhans Mice Pituitary Gland Anterior Cricetinae Internal medicine Insulin Secretion medicine Somatostatin receptor 3 Animals Insulin Somatostatin receptor 2 Somatostatin receptor 1 Amino Acid Sequence Receptors Somatostatin Receptor Cells Cultured Glucagon-like peptide 1 receptor Multidisciplinary Somatostatin receptor Membrane Proteins Glucagon Amides Rats Endocrinology Somatostatin Models Chemical Drug Design Growth Hormone hormones hormone substitutes and hormone antagonists |
| Zdroj: | Science. 282:737-740 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | Nonpeptide agonists of each of the five somatostatin receptors were identified in combinatorial libraries constructed on the basis of molecular modeling of known peptide agonists. In vitro experiments using these selective compounds demonstrated the role of the somatostatin subtype-2 receptor in inhibition of glucagon release from mouse pancreatic alpha cells and the somatostatin subtype-5 receptor as a mediator of insulin secretion from pancreatic beta cells. Both receptors regulated growth hormone release from the rat anterior pituitary gland. The availability of high-affinity, subtype-selective agonists for each of the somatostatin receptors provides a direct approach to defining their physiological functions. |
| Databáze: | OpenAIRE |
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