CALCITONIN-GENE-RELATED PEPTIDE INCREASES K-RAS EXPRESSION IN PRIMARYCULTURE CELL OF RAT SKELETAL-MUSCLE

Calcitonin gene-related peptide (CGRP) coexists with acetylcholine in the motor nerve terminal and may act as nerve-derived trophic factor f or muscle. In this report, we show that CGRP increases intracellular c AMP as a second messenger and induces K-ras expression, which is one o f the proto-oncogenes regulating cell function. In cultured rat myotub e, CGRP increased the intracellular cAMP level but did not change the cGMP content. The expressions of proto-oncogenes in cultured rat myotu be were measured by Northern blot analysis. The expressions of erbA, s rc, raf, sis, fos, myc, H-ras and K-ras were detected, but erbB and my b were not seen. CGRP increased solely K-ras expression accompanied wi th the increased expression of nicotinic acetylcholine receptor (AChR) alpha-subunit. These findings suggest that CGRP is a nerve-derived tr ophic factor controlling gene expressions in the skeletal muscle.