Role of cAMP in activation of ischemically sensitive abdominal visceral afferents

A number of metabolites produced during abdominal ischemia can stimulate an d/or sensitize visceral afferents. The precise mechanisms whereby these met abolites act are uncertain. Other studies have shown that the adenylate cyc lase-cAMP system may be involved in the activation of sensory neurons. Ther efore, we hypothesized that cAMP contributes to the activation of ischemica lly sensitive abdominal visceral afferents. Single-unit activity of abdomin al visceral C fibers was recorded from the right thoracic sympathetic chain in anesthetized cats before and during 7 min of abdominal ischemia. Forty- six percent of ischemically sensitive C fibers responded to intra-arterial injection of 8-bromo-cAMP (0.35-1.0 mg/kg), an analog of cAMP, with respons es during ischemia increasing from 0.50 +/- 0.06 to 0.84 +/- 0.08 impulses/ s (P < 0.05, n = 11 C fibers). Conversely, an inhibitor of adenylate cyclas e, 2',5'-dideoxyadenosine (DDA; 0.1 mg/kg iv), attenuated ischemia-induced increase in activity of afferents from 0.66 +/- 0.10 to 0.34 +/- 0.09 impul ses/s (P < 0.05; n = 8). Furthermore, whereas exogenous PGE(2) (3-4 mu g/kg ia) augmented the ischemia-induced increase in activity of afferents (P < 0.05, n = 10), treatment with DDA (0.1 mg/kg iv) substantially reduced the increase in discharge activity of afferents during ischemia, which was augm ented by PGE(2) (1.45 +/- 0.24 vs. 0.70 +/- 0.09 impulses/s, -DDA vs. +DDA; P < 0.05) in six fibers. A time control group (n = 4), however, demonstrat ed similar increases in the activity of afferents with repeated administrat ion of PGE(2). These data suggest that cAMP contributes to the activation o f abdominal visceral afferents during ischemia, particularly to the action of PGs on activation and/or sensitization of these endings.