SIGNAL-TRANSDUCTION IN ACTIVATION OF ISCHEMICALLY SENSITIVE ABDOMINALVISCERAL AFFERENTS - ROLE OF PKC

Abdominal ischemia reflexly activates the cardiovascular system by sti mulating abdominal visceral afferent nerve endings. Whereas many ische mic metabolites responsible for activating these nerves have been iden tified (e.g., bradykinin), their precise mechanism of action is unclea r. Protein kinase C (PKC) is an important part of the signal transduct ion process underlying the action of metabolites such as bradykinin an d is a regulator of neuronal activity. Therefore, we hypothesized that PKC contributes to stimulation of ischemically sensitive abdominal vi sceral afferents. Single-unit activity was recorded from the right tho racic sympathetic chain of anesthetized cats. Exogenous activation of PKC using phorbol 12,13-dibutyrate (PDBu, 5 mu g/kg ia) increased the impulse activity of ischemically sensitve 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 m esenteric ischemia. Inhibition of PKC using PKC-(19-36) (20 mu g/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-(1 9-36) (20 mu g/kg iv) reduced the response of ischemically sensitive C fibers to bradykinin (0.5-1.0 mu g/kg ia) from 1.18 +/- 0.20 to 0.66 +/- 0.14 impulses/s (n = 13, P < 0.05). These results indicate that PK C contributes to activation of abdominal visceral afferents during isc hemia and specifically to part of the bradykinin-induced activation of these afferents.