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

• Published in: Journal of applied physiology (1985) Vol. 98; no. 2; pp. 655 - 662
• Main Authors: Hinkle, Richard T, Donnelly, Elizabeth, Cody, David B, Sheldon, Russell J, Isfort, Robert J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.02.2005; American Physiological Society
• Subjects: Adaptation, Physiological; Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Mice; Muscle Contraction; Muscle, Skeletal - drug effects; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Atrophy - pathology; Muscular Atrophy - physiopathology; Muscular system; Nervous system; Organ Size - drug effects; Peptides; Peptides, Cyclic - administration & dosage; Receptors, Vasoactive Intestinal Peptide - agonists; Receptors, Vasoactive Intestinal Peptide - metabolism; Receptors, Vasoactive Intestinal Peptide, Type II; Rodents; Steroids; Striated muscle. Tendons; Vasoactive Intestinal Peptide - administration & dosage; Vertebrates: osteoarticular system, musculoskeletal system; Agonist; Rat; Force; Rodentia; Activation; Striated muscle; anti-atrophy; Atrophy; Vertebrata; Mammalia; Mouse; VPAC2 receptor; vasoactive intestinal peptide receptor; Morphometry; Mechanism of action; muscle hypertrophy; Muscle mass
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00736.2004

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 [K 15 ,R 16 ,L 27 ]VIP(1-7) GRF(8-27)-NH 2 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 Address for reprint requests and other correspondence: R. J. Isfort, Research Division, Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Rd., Mason, OH 45040-9317 (E-mail: isfort.rj{at}pg.com )