Abstract
Different modes by which Ca 2+, entering the nerve terminal, promotes transmitter secretion as well as the ability of protons to release neuropeptides, have been shown in peripheral endings of capsaicin-sensitive afferents. We have studied these two aspects in the central endings of these neurons by measuring the release of calcitonin-gene related peptide-like immunoreactivity (CGRP-LI) from slices of the dorsal half of the guinea pig spinal cord. Altough capsaicin (1 μM) released both CGRP-LI and substance P-like immunoreactivity (SP-LI), CGRP-LI was chosen as the sole suitable marker of peptides released from central terminals of capsaicin-sensitive afferents, since after in vitro desensitization to capsaicin (1μM capsaicin for 20 min), high K + (80 mM) failed to evoke CGRP-LI release, whereas SP-LI release was still observed. The capsaicin (1 μM)-evoked CGRP-LI release was entirely dependent on extracellular Ca 2+. It was unaffected by 0.3 μM tetrodotoxin (TTX), slightly reduced by 0.1 μM ω-conotoxin (CTX) and blocked by 10 μM Ruthenium red (RR). The Ca 2+-dependent K + (80 mM)-evoked CGRP-LI release was unaffected by TTX, markedly reduced by CTX and only moderatedly inhibited by RR. Low pH (pH 5) produced a remarkable increase in CGRP-LI outflow that was abolished after exposure to capsaicin, reduced by about 50% in Ca 2+-free medium and unaffected by TTX (0.3 μM). The Ca 2+-dependent component of the proton-evoked CGRP-LI release was abolished in the presence of RR (10 μM) and slightly inhibited by CTX (0.1 μM). The mode by which capsaicin or high K + promote Ca 2+ entry into the central endings of capsaicin-sensitive afferents, and hence promote neuropeptide release may be distinguished on a pharmacological basis. Protons release CGRP in the spinal cord by a mechanism that shares a common pathway with that activated by capsaicin.
Published Version
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