NON-GENOMIC SIGNAL-TRANSDUCTION PATHWAY OF VITAMIN-D IN MUSCLE

The secosteroid hormone 1,25(OH)(2)-vitamin D-3 rapidly activates voltage-dependent Ca2+ channels of the L-type in skeletal and cardiac muscle cells by a non-genomic mechanism which involves guanine nucleotide binding (G) protein-mediated stimulation of the adenylate cyclase/cAMP/protein kinase A messenger system. Modifications in calmodulin intracellular distribution induced by PKA-dependent membrane protein phosphorylation may participate in the fast regulation of muscle Ca2+ influx by 1,25(OH)(2)D-3. The protein kinase C pathway also plays a role modulating 1,25(OH)(2)D-3 signal transduction in muscle by cross-talk with the PKA system. The hormone sequentially activates phospholipases C and D providing diacylglycerol for PKC activation and inositol triphosphate for intracellular Ca2+ mobilization. In addition, 1,25(OH)(2)D-3 rapidly stimulates phospholipase A(2) generating arachidonic acid for the eicosanoid pathway. Specificity of hormone effects suggests that binding to a muscle membrane-bound receptor mediates these events.