Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses

Low pH medium has been shown to activate the ‘efferent’ function of capsaicin-sensitive primary sensory neurons. Calcitonin gene-related peptide (CGRP) is released from capsaicin-sensitive afferents of guinea-pig superior sagittal and transverse sinuses (SSTS), by capsaicin or bradykinin. Here, we report that low pH medium produces a remarkable release of CGRP from SSTS, which was dependent on the concentration of hydrogen ions of the medium (pH 7-5). Moreover, the pH 5-evoked release of CGRP-Ll was markedly reduced (by about 70 %) in a calcium-free medium containing 1 mM EDTA or abolished in samples pre-exposed to 10 μM capsaicin. The present observation that lowering of the pH promotes release of a powerful vasoactive peptide from perivascular capsaicin-sensitive sensory nerves may have some relevance in the pathophysiology of brain injury and migraine headaches.