Corticotropin-releasing factor-induced production of cyclic AMP by human peripheral blood immunocytes

• Published in: Immunology letters Vol. 35; no. 3; pp. 239 - 245
• Main Authors: Singh, Vijendra K., Leu, Sy-Jye Christine
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.1993; Elsevier
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Adult; Biological and medical sciences; Calcium Channel Blockers - immunology; cAMP; Cell physiology; Corticotropin-releasing factor; Corticotropin-Releasing Hormone - immunology; Cyclic AMP - biosynthesis; Fundamental and applied biological sciences. Psychology; Humans; Immunomodulation; Isoquinolines - immunology; Leukocytes, Mononuclear - immunology; Lymphocytes - immunology; Molecular and cellular biology; Monocytes - immunology; Neuroendocrine-immune axis; Neurohormone; Neuropeptide; Piperazines - immunology; Protein Kinase Inhibitors; Signal transduction; Signal Transduction - immunology; Sulfonamides; Neuroendocrine-immune axis; Corticotropin-releasing factor; Neurohormone; cAMP; Immunomodulation; Neuropeptide; Human; Signal transduction; Mononuclear cell; Calcium; Peptide hormone; ACTH-RH; Second messenger; Cyclic AMP; Biosynthesis; Hormone releasing factor; Biological activity
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/0165-2478(93)90189-9

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 α-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 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.