Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2.
Proc Natl Acad Sci U S A
; 95(18): 10836-41, 1998 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-9724791
ABSTRACT
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 microgram/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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzimidazoles
/
Receptors, Somatostatin
/
Molecular Mimicry
/
Indoles
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
1998
Document type:
Article
Affiliation country: