The cAMP-mediated protein kinase signal transduction pathway is involved in the pyrogenic effect of CRH in rats

OBJECTIVE: To determine whether the cyclic adenosine monophosphate (cAMP) mediated protein kinase signal transduction pathway is involved in the pyrogenic action of corticotropin releasing hormone (CRH) in rats. METHODS: Corticotropin releasing hormone, 2',3'-dideoxyadenosine (DDA) and adenosine-3',5'-(cyclic) monophosphorothionate, Rp-Isomer (Rp-cAMPS), were administered intracerebroventricularly (i.c.v.). The colonic temperature was measured using a thermistor, and the content of cAMP in the hypothalamus was determined by radioimmunoassay. Hypothalamic incubation was used to assess the effects of CRH on the content of cAMP in the hypothalamus in vitro. RESULTS: Microinjection (i.c.v.) of CRH (2.5 micrograms, 5.0 micrograms and 10 micrograms) caused increases in colonic temperature and the hypothalamus cAMP level in conscious rats. CRH increased hypothalamus cAMP level in vitro. The pyrogenic effects of CRH were abolished or markedly inhibited by prior injection (i.c.v.) of an adenylate cyclase inhibitor, DDA (30 micrograms), or an inhibitor of cAMP-dependent protein kinase, Rp-cAMPS (15 micrograms). CONCLUSION: cAMP mediates the pyrogenic action of centrally administered of CRH in rats, and protein kinase A may play an important role in the central CRH-induced fever. The cAMP-dependent protein kinase signal transduction pathway may be involved in the central mechanisms of the pyrogenic action of CRH in rats.