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 mumol/l, the EC50 was 0.17 mumol/l. Pre-exposure of tissues to capsaicin (0.1-1.0 mumol/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 mumol/l, capsaicin was less effective to inhibit the subsequent K(+)-evoked release than that evoked by a second capsaicin exposure. Pre-exposure to 1 mumol/l capsaicin completely prevented subsequent K(+)- or capsaicin-evoked release of CGRP-IR. Exposure of the preparation to capsaicin (0.3 mumol/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 mumol/l for 5 min) of capsaicin at 37 degrees C. Comparison of the desensitizing effect of 0.3 and 0.1 mumol/l capsaicin at 18 degrees C and 37 degrees C, respectively, showed significant inhibition of desensitization at 18 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Amann
R
R
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D013696:Temperature; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism
D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D002118:Calcium