| Autor: |
I, Gozes, G, Lilling, R, Glazer, A, Ticher, I E, Ashkenazi, A, Davidson, S, Rubinraut, M, Fridkin, D E, Brenneman |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
The Journal of pharmacology and experimental therapeutics. 273(1) |
| ISSN: |
0022-3565 |
| Popis: |
To distinguish vasoactive intestinal peptide (VIP) receptors in the brain-mediating neurotransmission and neurotrophism, potent VIP analogues were designed. Using a single amino acid substitution and the addition of a fatty acyl moiety, an analogue was devised that exhibited both a 100-fold greater potency than VIP and specificity for a VIP receptor associated with neuronal survival. This VIP agonist increased neuronal survival via a cAMP-independent mechanism. Identical chemical modification of a prototype VIP antagonist (Met-Hybrid, Neurotensin6-11-VIP7-28) also resulted in a 100-fold greater potency in blocking VIP-mediated increases in neuronal survival. Blockade of circadian activity rhythms was limited to VIP antagonists that could inhibit VIP-mediated increases in cAMP. These lipophilic peptides provide novel tools in receptor discrimination and drug design. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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