The 'efferent' function of capsaicin-sensitive nerves: ruthenium red discriminates between different mechanisms of...

We have investigated the ability of Ruthenium Red, an inorganic dye with calcium entry blocking properties, to interfere with the 'efferent' function of capsaicin-sensitive sensory nerves. These nerves were activated in the guinea-pig isolated bronchus (atropine in the bath) or left atria (reserpine-pretreated animals, atropine in the bath) by electrical field stimulation or with capsaicin. Both stimuli produced a contraction of the bronchus and a positive inotropic response in the atria, responses which are mediated by endogenous neuropeptides (tachykinins in the bronchus, calcitonin gene-related peptide in the atria) released from sensory nerves. Ruthenium Red (10 microM for 20 min in both cases) selectively inhibited the responses produced by the administration of capsaicin, while leaving the responses to electrical field stimulation unaffected. Likewise, the bronchoconstrictor response to exogenous neurokinin A and the atrial positive inotropic response to calcitonin gene-related peptide were unaffected by Ruthenium Red. A prejunctional site of action of Ruthenium Red was confirmed in release experiments where the dye strongly inhibited the capsaicin-evoked outflow of calcitonin gene-related peptide, which is taken as a marker of activation in sensory nerves. Together with other observations, these findings support the concept that there are two independent mechanisms for activating the 'efferent' function of sensory nerves, one of which is activated by capsaicin and is Ruthenium Red-sensitive but omega-conotoxin-resistant, while the other is activated by propagated action potentials (field stimulation) and is omega-conotoxin-sensitive and Ruthenium Red-resistant.