Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with regulatory influences on immune and inflammatory responses and early B lymphocyte differentiation. Little is known about its cellular mechanisms. These studies examined whether CGRP induces c-fos. CGRP induced a transient concentration-dependent increase in c-fos in a CGRP receptor expressing pre-B cell line, 70Z/3. CGRP did not induce c-jun, jun B or jun D. A protein kinase A (PKA) inhibitor blocked c-fos induction by CGRP, suggesting that the mechanism depends on cAMP induction of PKA. CGRP induced AP-1 binding activity in the nucleus, indicating that CGRP regulates expression of specific target genes. CGRP also induced c-fos in B220(+) enriched cells from bone marrow. These results suggest that regulatory influences of CGRP on early B cells and in other tissues can involve a cAMP/PKA, c-fos/AP-1-dependent pathway for regulation of specific genes.
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