Evidence that CGRP and cAMP increase transcription of AChR alpha-subunit gene, but not of other subunit genes.

Calcitonin gene-related peptide (CGRP) is present in embryonic chick motoneurons and their terminals during myogenesis. We have studied the effect of CGRP on the expression of mRNA encoding the four subunits (alpha, beta, gamma, delta) of ACh receptors in cultured myotubes derived from embryonic chicks. Northern blot analysis showed that treatment with 10(-7) M CGRP caused an increase in ACh receptor alpha-subunit mRNA expression but did not affect the expression of beta-, gamma-, or delta-subunit mRNAs. In addition, CGRP treatment caused an increase in the expression of unspliced alpha-subunit RNA, suggesting that CGRP increases transcription of the alpha-subunit gene. The effect of CGRP on alpha-subunit gene transcription was mimicked by forskolin, and both CGRP and forskolin increased the levels of intracellular cAMP. We infer that the effect of CGRP on alpha-subunit gene transcription is likely to be mediated by the CGRP-induced rise in intracellular cAMP.