Effects of ruthenium red and capsazepine on C-fibres in the rabbit iris.

1. We have investigated the effects of ruthenium red and capsazepine on a C-fibre-smooth muscle preparation (the rabbit isolated iris sphincter muscle). 2. Like capsaicin, ruthenium red and capsazepine were found to produce contractions in a concentration-dependent manner. C-fibre activation was held to be responsible since the contractions could be inhibited by tachykinin receptor blockade. 3. Both ruthenium red and capsazepine inhibited capsaicin-induced contractions concentration-dependently; the pIC50 values were 5.1 and 4.9, respectively. The contractions induced by bradykinin, which, like capsaicin, acts by releasing tachykinins from C-fibres, were also inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.1 and 4.6, respectively. 4. Electrically evoked, tachykinin-mediated contractions were inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.3 and 4.5, respectively. 5. The contractile response to neurokinin A (NKA) was inhibited by capsazepine (and by capsaicin), but not by ruthenium red, in a concentration-dependent manner; the pIC50 value was 4.3. 6. The results suggest that, besides their ability to antagonize capsaicin, ruthenium red and capsazepine possess a weak capsaicin-like effect. Conceivably, capsazepine interacts with binding sites for capsaicin, acting as a partial agonist/antagonist, while ruthenium red interacts with capsaicin-operated cation channels. The inhibition of electrically evoked- or bradykinin-induced responses by capsazepine and ruthenium red suggests that capsaicin/capsazepine binding sites and capsaicin-operated cation channels play a role in the process of transmitter release in response not only to capsaicin but also to other C-fibre stimuli. In addition, capsazepine (and capsaicin) may affect smooth muscle non-specifically since the response to NKA was also inhibited by this drug. The fact that ruthenium red did not affect the response to NKA provides further evidence that ruthenium red acts in a mode different from that ofcapsazepine.