16 However, their differential binding preference for CRHR1 and CRHR2 suggests that CRH and Ucn II have different functions in the stress response. The localization of Ucn III (Figure 1B) 14,17 in the brain is different from that of CRH,29 Ucn,20 and Ucn II.16 This latest discovered member of the CRH neuropeptide family is found in
the median preoptic area, the rostral perifornical area (a region lateral from the PVN in the hypothalamus), the posterior part of the BNST, and the medial nucleus of the amygdala (Figure 1B).14 Until now, unfortunately, no Inhibitors,research,lifescience,medical Fos studies have been selleck compound published with Ucn III. It is relevant to note though that parts of the perifornical Inhibitors,research,lifescience,medical region project into the (CRHR2-rich) LS, an area in
which both Ucn-ir and piscine urotensin I-ir can be found.20 However, within the LS, Ucn-ir and urotensin I are differentially localized with Ucn-ir prevailing in the medial aspect of the iLS and urotensin I-ir concentrating in the ventrolateral aspect of this nucleus, ic, the site where CRH-R2 mRNA is also found (see also above). It may be speculated that, given the structural relationship between urocortins and urotensin, the immunoreactivity in the ventrolateral aspect of the iLS as revealed with the piscine urotensin I antiserum may actually be Ucn III. Recently, Ucn III-ir fibers were indeed found in this region of the LS (and Inhibitors,research,lifescience,medical in the VMH), which corresponds well with the sites of CRHR2 mRNA expression (P. E. Sawchenko, personal communication). Inhibitors,research,lifescience,medical CRHR1 and CRHR2 in anxiety, sleep/electroencephalographic regulation and HPA axis control: significance for clinical anxiety and depression In recent years, many studies have been performed
to delineate the specific role of CRHR1 and CRHR2 in stress-related physiological and behavioral processes to gain insight into anxiety and Inhibitors,research,lifescience,medical major depressive disorders. Various strategies have been employed including pharmacological approaches, mutant mice with functional deletions in one of the receptors, and antisense oligodeoxynucleotide (ODN) technology. These investigations have provided insight into the complexity of the contributions of CRHR1 and CRHR2 in the regulation of emotional behavior, HPA axis activity, and GPX6 autonomic function. For some processes, the roles of CRHR1 and CRHR2 seem clear, whereas for others they still need to be clarified. Anxiety CRH is highly implicated in the regulation of anxietyrelated behavior and is thought to play a pivotal role in anxiety and depressive disorders.24,30,31 Several lines of evidence point to the participation of CRHR1 in the effects of CRH. First, CRHR1 binds CRH with high affinity, in contrast to CRHR2. Second, CRHRl-deficient mice show decreased anxiety-related behavior.32,33 Third, transgenic mice overexpressing CRH show increased anxiety-related behavior34 (van Gaalen et al, unpublished data).