LACTIC-ACID POTENTIATES BRADYKININ-INDUCED AND LOW-PH-INDUCED RELEASEOF CGRP FROM RAT SPINAL-CORD SLICES

Previous data from our laboratory have shown that calcitonin gene-rela ted peptide (CGRP) is released into the circulation during pathogenesi s of endotoxic, hemorrhagic, and septic shock and appears to mediate i n part the vascular problems of shock. Elevations in the levels of bra dykinin (BK) and lactic acid and lowering of tissue pH also occur duri ng shock and could be involved in CGRP release. In the present study, we have tested whether lactic acid, alone or in combination with BK or low pH, triggers release of CGRP-like immunoreactivity (CGRP-LI) from sensory nerves, using rat spinal cord slices as a tissue model. Lower ing media pH from 7.4 to less than or equal to 6.0 increased the relea se of CGRP-LI. Lactic acid (5 and 10 mM) by itself elevated CGRP-LI re lease from a control of 6.89 +/- 0.95 to 57.2 +/- 8.2 and 116 +/- 13 p g/mg protein, respectively. The combination of pH 6.0 and lactic acid (5 or 10 mM) caused more than additive stimulation of CGRP-LI release. BK (50 or 100 mu M) elevated CGRP-LI release, which was greatly enhan ced by lactic acid (2.5 or 5 mM). The data indicate that lactic acid p otentiates BK- and low-pH-induced release of CGRP from sensory nerves in spinal cord. Similar mechanisms may occur at peripheral ends of sen sory nerves, contributing to CGRP release during septic shock and othe r conditions with elevated lactic acid levels (e.g., strenuous exercis e and tissue ischemia).