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Activation of the vasoactive intestinal peptide 2 receptor modulates normal and atrophying skeletal muscle mass and force

Research Division, Procter & Gamble Pharmaceuticals, Mason, Ohio

Submitted 14 July 2004 ; accepted in final form 5 September 2004

Of the two known vasoactive intestinal peptide receptors (VPAC1R and VPAC2R), the VPAC2R is expressed in skeletal muscle. To evaluate the function of the VPAC2R in the physiological control of skeletal muscle mass, we utilized the VPAC1R selective agonist [K¹⁵,R¹⁶,L²⁷]VIP(1-7) GRF(8-27)-NH₂ and the VPAC2R selective agonist Ro-25-1553 to treat mice and rats undergoing either nerve damage-, corticosteroid-, or disuse-induced skeletal muscle atrophy. These analyses demonstrated that activation of VPAC2R, but not VPAC1R, reduced the loss of skeletal muscle mass and force during conditions of skeletal muscle atrophy resulting from corticosteroid administration, denervation, casting-induced disuse, increased skeletal muscle mass, and force of nonatrophying muscles. These studies indicate that VPAC2R agonists may have utility for the treatment of skeletal muscle-wasting diseases.

anti-atrophy; muscle hypertrophy; vasoactive intestinal peptide receptor