The effects of capsaicin upon electrogenic ion transport in rat descending colon.

Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 microM) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20-30 min. Repeated applications of 3 microM capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i.e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as "non-responders", 3 microM capsaicin did not elicit a secretory response. No desensitization of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response. Tetrodotoxin (100 nM), hexamethonium (10 microM), and yohimbine (50 microM) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 microM) abolished the secretory response to 3 microM capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 microM substance P (SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 microM capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues.