Details

Autor(en) / Beteiligte

• Yang, Lihu
• Berk, Scott C.
• Rohrer, Susan P.
• Mosley, Ralph T.
• Guo, Liangqin
• Underwood, Dennis J.
• Arison, Byron H.
• Birzin, Elizabeth T.
• Hayes, Edward C.
• Mitra, Sudha W.
• Parmar, Rupa M.
• Cheng, Kang
• Wu, Tsuei-Ju
• Butler, Bridgette S.
• Foor, Forrest
• Pasternak, Alexander
• Pan, Yanping
• Silva, Maria
• Freidinger, Roger M.
• Smith, Roy G.
• Chapman, Kevin
• Schaeffer, James M.
• Patchett, Arthur A.

Titel

Synthesis and Biological Activities of Potent Peptidomimetics Selective for Somatostatin Receptor Subtype 2

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-09, Vol.95 (18), p.10836-10841

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1998

Quelle

MEDLINE

Beschreibungen/Notizen

• A series of nonpeptide somatostatin agonists which bind selectively and with high affinity to somatostatin receptor subtype 2 (sst2) have been synthesized. One of these compounds, L-054,522, binds to human sst2 with an apparent dissociation constant of 0.01 nM and at least 3,000-fold selectivity when evaluated against the other somatostatin receptors. L-054,522 is a full agonist based on its inhibition of forskolin-stimulated adenylate cyclase activity in Chinese hamster ovary-K1 cells stably expressing sst2. L-054,522 has a potent inhibitory effect on growth hormone release from rat primary pituitary cells and glucagon release from isolated mouse pancreatic islets. Intravenous infusion of L-054,522 to rats at 50 μ g/kg per hr causes a rapid and sustained reduction in growth hormone to basal levels. The high potency and selectivity of L-054,522 for sst2 will make it a useful tool to further characterize the physiological functions of this receptor subtype.