Brain corticotropin-releasing hormone receptors on neurons and astrocytes

Abstract

Corticotropin-releasing hormone (CRH) exerts many potent effects within brain and is considered an important brain neuroregulator. CRH acts via receptors that are widely distributed throughout brain which exhibits highest CRH receptor concentrations in extrahypothalamic regions. We have previously characterized CRH receptors in heterogeneous extrahypothalamic forebrain cell cultures consisting of neurons and glia, and have shown them to exhibit similar kinetic and pharmacological characteristics as CRH receptors in pituitary and in situ brain. However, it is not known whether CRH receptors are present on neurons, glia or both. We tested the hypothesis that CRH receptors are present on neurons in extrahypothalamic forebrain cell cultures derived from day 17–18 fetal rats by characterizing receptors in predominantly neuronal (N), glial/astrocytic (G) cultures and mixed (M) cultures. Mean CRH receptor concentrations (fmol/mg protein) in N (10.4), G (9.4), and M (9.8) cultures were similar. Following Scatchard analyses derived from competition curves, all cell populations exhibited similar mean high-affinity/ low-capacity ( K d = 1.0–1.9 nM; B max = 183–388 fmol/mg protein) and low-affinity/high-capacity ( K d = 92–104 nM; B max = 2034–5008 fmol/mg protein) classes of binding sites. In conclusion: (1) Neurons and astrocytes in fetal extrahypothalamic brain cell cultures contain CRH receptors which exhibit similar concentrations and similar kinetic characteristics. (2) These observations suggest that biological effects of CRH in brain could be mediated via actions on neurons and/or glial astrocytes.