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 HA1004, indicating a role for Ca(2+)-signalling. Based on these findings, it is concluded that cAMP and/or Ca2+ play a second messenger role in the CRF signal transduction pathway.
Singh
V K
VK
Department of Biology, Utah State University, Logan 84322-6800.
Leu
S J
SJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000328:Adult; D002121:Calcium Channel Blockers / Q000276:immunology; D003346:Corticotropin-Releasing Hormone / Q000276:immunology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D007546:Isoquinolines / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010879:Piperazines / Q000276:immunology; D047428:Protein Kinase Inhibitors; D015398:Signal Transduction / Q000276:immunology; D013449:Sulfonamides
D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003346:Corticotropin-Releasing Hormone; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D000242:Cyclic AMP