RELEASE OF CALCITONIN GENE-RELATED PEPTIDE-LIKE (CGRP-LI) IMMUNOREACTIVITY FROM RAT ISOLATED SOLEUS MUSCLE BY LOW PH, CAPSAICIN AND POTASSIUM

Capsaicin (10-mu-M), KCl (80 mM) or superfusion with a low pH medium (pH 5 or 6) produced a significant increase of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) outflow from the superfused rat isolated soleus muscle. CGRP-LI outflow produced by capsaicin or pH 5 medium was totally abolished in a calcium free medium containing EDTA (1 mM) and the effect of pH 5 medium was prevented by a previous application of capsaicin. Ruthenium red (10-mu-M) produced a marked inhibition of CGRP-LI release produced by capsaicin or pH 5 medium (69 and 84%, resp.), without affecting that evoked by KCl. These findings demonstrate that protons activate capsaicin-sensitive primary afferents in rat skeletal muscle through a Ruthenium red-sensitive mechanism. Proton-induced CGRP-LI release in skeletal muscle could be of relevance during exercise and/or skeletal muscle ischemia.