The mechanism of neuropeptide secretion induced by bradykinin from capsaicin-sensitive afferents was studied in guinea-pig atria. Both the inotropic response induced by bradykinin (0.1 microM) in the electrically driven isolated guinea-pig left atria and the bradykinin (10 microM)-induced release of calcitonin gene-related peptide calcitonin gene-related peptide-like immunoreactivity from slices of guinea-pig atria were abolished in vitro by capsaicin pretreatment or in the presence of indomethacin. Bradykinin-induced calcitonin gene-related peptide-like immunoreactive release was unaffected by tetrodotoxin (0.3 microM), the protein kinase C inhibitor, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (30 microM), nefedipine (1 microM) or Ruthenium Red (10 microM). It was significantly reduced by 79% in a Ca2(+)-free medium and by 52% in the presence of 0.1 microM omega-conotoxin (fraction GVIA). It is proposed that bradykinin releases calcitonin gene-related peptide from capsaicin-sensitive afferents in guinea-pig atria, via prostanoid generation. This mode of activation of the "efferent" function of capsaicin-sensitive nerves appears to be distinct from those produced by capsaicin or electrical field stimulation as they have been characterized in previous works. In fact, the bradykinin activation of capsaicin-sensitive afferents is not affected by tetrodotoxin and Ruthenium Red, but is partially sensitive to the selective blocker of N-type Ca2(+)-channels, omega-conotoxin.