ARGININE-VASOPRESSIN INDUCES DIFFERENTIATION OF SKELETAL MYOGENIC CELLS AND UP-REGULATION OF MYOGENIN AND MYF-5

The neurohypophyseal nonapeptide arginine(8)-vasopressin (AVP) induces phosphoinositide turnover and calcium and pH changes in skeletal myog enic cells in culture. In order to investigate the effect of AVP on sk eletal myogenesis, we examined the effect of this hormone on prolifera ting mononucleated L6 myoblast cultures. Addition of AVP to the medium resulted in the formation of much larger myotubes than those formed i n its absence and in a significant increase (2.2-fold) of the percenta ge of fusion within 3-4 days of treatment. The effect of AVP was dose dependent, in the 10 nM to 1 mu M range, and was observed also in prim ary cultures of mouse satellite cells. The rate of growth of L6 cells was not affected by AVP treatment. The induction of morphological diff erentiation by AVP correlated with an increased expression of muscle-s pecific gene products, such as myosin, and an increased number of acet ylcholine receptor sites. The accumulation of mRNA transcripts of the acetylcholine receptor subunits was also enhanced by AVP. The mechanis m involved in the myogenic action of AVP was investigated. Using AVP-r elated peptides and antagonists, we found that a specific chemical str ucture is required and that V1 receptors probably mediate the effect o n myogenesis. Expression of muscle-specific transcription factor genes Myf-5 and myogenin and their products are strongly upregulated by AVP . Our findings support the hypothesis that AVP may represent a novel p hysiological modulator of skeletal muscle differentiation through its action on muscle regulatory genes.