| Target Validation Information | |||||
|---|---|---|---|---|---|
| TTD ID | T86364 | ||||
| Target Name | Vasoactive intestinal polypeptide receptor 1 (VIPR1) | ||||
| Type of Target |
Clinical trial |
||||
| Drug Potency against Target | Vasoactive intestinal peptide | Drug Info | IC50 = 1 nM | [3] | |
| Vasoactive intestinal peptide | Drug Info | IC50 = 4.9 nM | [1] | ||
| Action against Disease Model | Vasoactive intestinal peptide | Drug Info | We performed the studies on the Kir6.1/SUR2B channel expressed in HEK293 cells. We found that the channel was strongly activated by VIP. Through endogenous VIP receptors, the channel activation was reversible and dependent on VIP concentrations with the midpoint-activation concentration approximately 10 nM. The channel activation was voltage-independent and could be blocked by KATP channel blocker glibenclamide. In cell-attached patches, VIP augmented the channel open-state probability with modest suppression of the single channel conductance. The VIP-induced Kir6.1/SUR2B channel activation was blocked by PKA inhibitor RP-cAMP. Forskolin, an adenylyl cyclase activator, activated the channel similarly as VIP. The effect of VIP was further evident in the native tissues. In acutely dissociated mesenteric vascular smooth myocytes, VIP activated the KATP currents in a similar manner as in HEK293 cells. In endotheli uM-free mesenteric artery rings, VIP produced concentration-dependent vasorelaxation that was attenuated by glibenclamide. | [2] | |
| References | |||||
| REF 1 | Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69. | ||||
| REF 2 | PKA-dependent activation of the vascular smooth muscle isoform of KATP channels by vasoactive intestinal polypeptide and its effect on relaxation o... Biochim Biophys Acta. 2008 Jan;1778(1):88-96. | ||||
| REF 3 | Vasoactive intestinal peptide (VIP)1 receptor. Three nonadjacent amino acids are responsible for species selectivity with respect to recognition of peptide histidine isoleucineamide. J Biol Chem. 1996 May 31;271(22):12795-800. | ||||
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