Potency of binding affinity and activity at CRF1 and CRF2 receptors
Ki is the equilibrium dissociation constant of the unlabeled ligand for the receptor, and Ki of oCRF for CRF1 receptors was calculated per the peptide's ability to displace 125I-Tyr0-oCRF; other Ki values were calculated per the peptide's ability to displace 125I-Tyr0-sauvagine. EC50 is the concentration of the ligand that resulted in 50% of the maximal functional response of the ligand, with all activity potency (EC50) estimates based on cAMP accumulation assays.
CRF1 | CRF2 | ||||||
|---|---|---|---|---|---|---|---|
| Ki (Binding) | EC50 (cAMP) | Ki (Binding) | EC50 (cAMP) | ||||
| nM | |||||||
| mUcn 3 | >1000a | >1000a | 5.0b | 0.073b | |||
| oCRF | 2.2c | 0.42c | 16d | 130d | |||
| Stressin1-A | 1.7e | N.D.f | 222e | N.D.f | |||
↵ a Data are from murine CRF1 receptors expressed in COS-7 cells (Venihaki et al., 2004).
↵ b Data are from rat CRF2(a) receptors expressed in Chinese hamster ovary cells (Lewis et al., 2001).
↵ c Data are from rat CRF1 receptors expressed in human embryonic kidney cells (Rühmann et al., 1999).
↵ d Ki from rat olfactory bulb [CRF2(a) receptors]; EC50 from rat CRF2(b) receptors expressed in A7r5 cells (Hoare et al., 2005).
↵ e Data are from human CRF1 receptors and mouse CRF2(b) receptors expressed in Chinese hamster ovary cells (Rivier et al., 2007).
↵ f Although cAMP assays have not yet been performed (N.D.) for stressin1-A, it is similarly potent to oCRF in releasing adrenocorticotropin from dispersed anterior pituitary cells (a CRF1-mediated endpoint), and it does not reduce gastric emptying (10 μg/kg i.p.) or arterial blood pressure (10 μg/kg i.v.) in vivo (CRF2-mediated endpoints) at a dose that stimulates fecal output and diarrhea (CRF1-mediated endpoints) (Rivier et al., 2007).