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 invitro. 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-mu-mol/l, the EC50 was 0.17-mu-mol/l. Pre-exposure of tissues to capsaicin (0.1 - 1.0-mu-mol/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-mu-mol/l, capsaicin was less effective to inhibit the subsequent K+ -evoked release than that evoked by a second capsaicin exposure. Pre-exposure to 1-mu-mol/l capsaicin completely prevented subsequent K+- or capsaicin-evoked release of CGRP-IR. Exposure of the preparation to capsaicin (0.3-mu-mol/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-degrees-C, the capsaicin-evoked release of CGRP-IR was reduced to 20% of the value obtained by the same dose (0.3-mu-mol/l for 5 min) of capsaicin at 37-degrees-C. Comparison of the desensitizing effect of 0.3 and 0.1-mu-mol/l capsaicin at 18-degrees-C and 37-degrees-C, respectively, showed significant inhibition of desensitization at 18-degrees-C. Inhibition of desensitization was also observed when the amount of CGRP-IR, which was released during pre-exposure to capsaicin (0.3-mu-mol/l for 10 min) at 18-degrees-C, was 3-fold higher than that produced by pre-exposure to capsaicin (0.1-mu-mol/l for 5 min) at 37-degrees-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.