Lactic acid potentiates bradykinin- and low ph-induced release of
cgrp from rat spinal cord slices.
Wang, Xian, and Ronald R. Fiscus.
Institute of Vascular Medicine, The Third Hospital Beijing Medical
University, Beijing, 100083, P.R. China and Department of Physiology,
Faculty of Medicine The Chinese University of Hong Kong, Shatin, New
Territories, Hong Kong and Department of Physiology & Biophysics,
and Stroke Research Program, Sanders-Brown Center on Aging,
University of Kentucky College of Medicine, Lexington, KY 40536
APStracts 4:0058E, 1997.
Previous data from our laboratory have shown that calcitonin gene
-related peptide (CGRP) is released into the circulation during
pathogenesis of endotoxin, hemorrhagic and septic shock and appears
to mediate in part the vascular problems of shock. Elevations in the
levels of bradykinin (BK) and lactic acid and lowering of tissue pH
also occur during 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, trigger release of CGRP-like
immunoreactivity (CGRP-IL) from sensory nerves, using rat spinal cord
slices as a tissue model. Lowering media pH from 7.4 to 6.0 or lower
increased the release of CGRP-LI. Lactic acid (5 and 10 mM), by
itself, elevated CGRP-LI release from a control of 6.89+/-0.95 to
57.2+/-8.2 and 116+/-13 pg/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 enhanced by lactic acid (2.5 or 5 mM). The
data indicate that lactic acid potentiates BK- and low pH-induced
release of CGRP from sensory nerves in spinal cord. Similar
mechanisms may occur at peripheral ends of sensory nerves,
contributing to CGRP release during septic shock and other conditions
with elevated lactic acid levels (e.g. strenuous exercise and tissue
ischemia).
Received 17 December 1996; accepted in final form 26 February
1997.
APS Manuscript Number E617-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 March 1997