Corticotropin-releasing hormone (CRH) receptors in brain.

Abstract

Studies with iodine-125-labeled analogues of CRH have identified, characterized, and localized binding sites for CRH in rat and human brain. In addition, we have demonstrated that CRH stimulates cAMP production in various regions of the rat CNS. The significant regional differences in the stoichiometric relationship between receptor number and receptor-mediated cAMP production suggests that some populations of CRH receptors in brain may be functionally coupled to alternative signal transduction mechanisms. The autoradiographic data demonstrate that the distribution of CRH binding sites in the rat CNS corresponds well with the immunohistochemical distribution of CRH pathways and pharmacological sites of action of CRH in some areas of brain but not in others. The demonstration of an upregulation of CRH receptors following a decrease in CRH-IR in the cerebral cortex in Alzheimer's disease indicates a physiological relevance of the receptor site and is consistent with the concept that CRH acts as a neurotransmitter in regulating normal cortical functions. In addition, the data suggest that disease of this peptidergic system may be important in certain clinical manifestations of Alzheimer's disease. The effects of chronic atropine treatment to selectively upregulate CRH receptors in the cerebral cortex suggests an interaction between CRH and acetylcholine. These data provide further support for the proposed role of CRH as a neurotransmitter in the CNS. Furthermore, these studies demonstrating the characteristics of CRH receptors and CRH receptor-mediated signal transduction mechanisms in brain provide a means for better understanding the various functions of this neuropeptide under physiological and pathological conditions.