title: Activation of visceral afferents by bradykinin and ischemia: independent roles of PKC and prostaglandins.
abstract: 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 micrograms/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-(19-36), 20 micrograms/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-(19-36). 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.
authors.affiliation: Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California, Davis, 95616, USA.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Guo
authors.forename: J D
authors.initials: JD
authors.lastname: Symons
authors.forename: J C
authors.initials: JC
authors.lastname: Longhurst
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002415:Cats; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D014781:Viscera / Q000294:innervation*
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D011493:Protein Kinase C; D001920:Bradykinin