Figure 4.

CRF effects involve CRF₁ receptors but not the CRF-binding protein. Knockout mice were used to determine if CRF₁ or CRF₂ receptors were responsible for CRF actions on GIRK channels. CRF (100 nM) produced a significant enhancement of GIRK currents in CRF₂ receptor knockout mice, but this effect was absent in CRF₁ knockout mice (a, t₍₁₆₎ = 6.3, P<0.0001). Two pharmacological experiments conducted in wild-type mice also suggested that CRF₁ receptor activation is necessary for the CRF enhancement of GIRK currents (b). First, the CRF₂ agonist urocortin III (300 nM) did not enhance the amplitude of the dopamine IPSC. Second, the CRF₁ antagonist antalarmin (1–3 μM) had no effect on its own but did block the action of CRF (100 nM) on dopamine receptor-mediated currents. To test the involvement of the CRF-binding protein, an experiment was conducted with the CRF 6–33 peptide, a compound that has affinity for the binding protein but not CRF₁ receptors (c). CRF 6–33 (0.3–1 μM) had no effect on the amplitude of the dopamine IPSC and did not diminish the effect of CRF (100 nM).