Signal transduction in activation of ischemically sensitive abdominal visceral afferents: role of PKC.
Abdominal ischemia reflexly activates the cardiovascular system by stimulating abdominal visceral afferent nerve endings. Whereas many ischemic metabolites responsible for activating these nerves have been identified (e.g., bradykinin), their precise mechanism of action is unclear. Protein kinase C (PKC) is an important part of the signal transduction process underlying the action of metabolites such as bradykinin and is a regulator of neuronal activity. Therefore, we hypothesized that PKC contributes to stimulation of ischemically sensitive abdominal visceral afferents. Single-unit activity was recorded from the right thoracic sympathetic chain of anesthetized cats. Exogenous activation of PKC using phorbol 12, 13-dibutyrate (PDBu, 5 microg/kg ia) increased the impulse activity of ischemically sensitive C-fiber afferents from 0.04 +/- 0.01 to 0. 67 +/- 0.23 impulses/s (n = 11; P < 0.05). The influence of endogenous activation of PKC also was evaluated during 10 min of mesenteric ischemia. Inhibition of PKC using PKC-(19-36) (20 microg/kg iv) reduced ischemia-induced increases in afferent activity from 0.46 +/- 0.11 to 0.19 +/- 0.08 impulses/s (n = 7, P < 0.05). Moreover, PKC-(19-36) (20 microg/kg iv) reduced the response of ischemically sensitive C fibers to bradykinin (0.5-1.0 microg/kg ia) from 1.18 +/- 0.20 to 0.66 +/- 0.14 impulses/s (n = 13, P < 0. 05). These results indicate that PKC contributes to activation of abdominal visceral afferents during ischemia and specifically to part of the bradykinin-induced activation of these afferents.
Department of Internal Medicine, University of California, Davis, California 95616, USA.
Z L
ZL
Guo
L W
LW
Fu
J D
JD
Symons
J C
JC
Longhurst
D000005:Abdomen; D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002415:Cats; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D014781:Viscera / Q000098:blood supply / Q000294:innervation*
D004791:Enzyme Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D001920:Bradykinin