Desensitization of capsaicin-evoked neuropeptide release — Influence of Ca2+ and temperature
Capsaicin-induced stimulation and desensitization of neuropeptide release from primary afferent neurons was investigated in the rat urinary bladder in-vitro. The capsaicin (5 min contact time)-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was dose-dependent; threshold to produce detectable release was 0.1 µmol/l, the EC50 was 0.17 µmol/l.
Pre-exposure of tissues to capsaicin (0.1–1.0 µmol/l, 5 min contact time) caused a dose-dependent reduction of the amount of CGRP-IR which was released by a second exposure to capsaicin. At 0.1 and 0.3 µmol/l, capsaicin was less effective to inhibit the subsequent K+-evoked release than that evoked by a second capsaicin exposure. Pre-exposure to 1 µmol/l capsaicin completely prevented subsequent K+- or capsaicin-evoked release of CGRP-IR.
Exposure of the preparation to capsaicin (0.3µmol/l) in a Ca2+-free, EDTA-containing medium did not produce release of CGRP-IR. A subsequent stimulation with capsaicin in a 2.5 mmol/l Ca2+-containing superfusion solution was not less effective to release CGRP-IR than in tissues which had not been pre-exposed to capsaicin.
At 18°C, the capsaicin-evoked release of CGRP-IR was reduced to 20% of the value obtained by the same dose (0.3 µmol/l for 5 min) of capsaicin at 37°C.
Comparison of the desensitizing effect of 0.3 and 0.1 µmol/l capsaicin at 18°C and 37°C, respectively, showed significant inhibition of desensitization at 18°C. Inhibition of desensitization was also observed when the amount of CGRP-IR, which was released during preexposure to capsaicin (0.3 µmol/l for 10 min) at 18°C, was 3-fold higher than that produced by pre-exposure to capsaicin (0.1 µmol/l for 5 min) at 37°C.
The present results show that in a narrow range of concentrations, capsaicin induces “selective” desensitization which is entirely dependent on the presence of external Ca2+ — and which is attenuated at low temperature.
Key wordsCapsaicin Primary afferents Desensitization Temperature-dependency
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