We have shown that the cyclooxygenase (COX) and protein kinase C (PKC) systems both contribute to afferent activation in response to bradykinin (BK) and abdominal ischemia. Because the contribution from PKC to C fiber activation may depend, in part, on prostaglandin production, we hypothesized that an intact COX system is required for PKC-induced activation of ischemically sensitive abdominal visceral afferents by BK and abdominal ischemia. Single-unit activity of abdominal visceral C fibers was recorded from the right thoracic sympathetic chain of anesthetized cats. Three repeated injections of BK (1-2 µg/kg ia) produced similar increases in afferent activity from the baseline of 1.32 ± 0.24, 1.37 ± 0.32, and 1.41 ± 0.24 impulses/s (n = 5). In another group of animals (n = 5), the second and third BK injections were performed after COX inhibition (indomethacin; 5 mg/kg iv) and then combined COX + PKC inhibition [PKC-(1936), 20 µg/kg iv], respectively. Inhibition of COX reduced (P < 0.05) the afferent response to BK (0.59 ± 0.12 impulses/s) compared with the unblocked condition (1.14 ± 0.27 impulses/s), whereas combined COX + PKC inhibition further attenuated the increase from baseline (0.18 ± 0.09 impulses/s; P < 0.05). Similar results were obtained in a third group of cats when the antagonists were administered in reverse order (n = 7). In a fourth group of cats (n = 9) that were pretreated with indomethacin, ischemia increased afferent activity (0.78 ± 0.17 impulses/s). However, neural activity was attenuated (0.51 ± 0.14 impulses/s; P < 0.05) during a second bout of ischemia in the presence of indomethacin + PKC-(1936). These results suggest that the contribution from PKC to the activation of ischemically sensitive C fibers, particularly by BK, does not require an intact cyclooxygenase system.

sympathetic afferents; nociception; cat; phosphoinositide system; protein kinase C

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