CORTICOTROPIN-RELEASING FACTOR-INDUCED PRODUCTION OF CYCLIC-AMP BY HUMAN PERIPHERAL-BLOOD IMMUNOCYTES

The immunomodulating properties of a neuropeptide hormone, corticotropin-releasing factor (CRF), led us to investigate its effect on cAMP production by human peripheral blood mononuclear cells (MNC). In response to stimulation with CRF (100 nM), a statistically significant (P=0.019) increase occurred in the amount of cAMP produced by MNC. Purified monocytes, but not lymphocytes, also displayed a significant (P=0.01) increase (8- to 10-fold) in intracellular cAMP after treatment with CRF (100 nM). The antagonist alpha-helical CRF9-41 (100 nM) counteracted the cAMP increase induced by CRF (100 nM). The CRF-induced cAMP production was augmented by pretreatment of MNC with a cAMP-dependent protein kinase (PKA) peptide inhibitor (PI20), but was virtually unaffected by the protein kinase C (PKC) inhibitor H7, suggesting a role for cAMP signalling. Moreover, the CRF-stimulated cAMP level was reduced to baseline by intracellular Ca2+ antagonist HA 1004, indicating a role for Ca2+-signalling. Based on these findings, it is concluded that cAMP and/or Ca2+ play a second messenger role in the CRF signal transduction pathway.