Role of cAMP in activation of ischemically sensitive abdominal visceral afferents.
A number of metabolites produced during abdominal ischemia can stimulate and/or sensitize visceral afferents. The precise mechanisms whereby these metabolites act are uncertain. Other studies have shown that the adenylate cyclase-cAMP system may be involved in the activation of sensory neurons. Therefore, we hypothesized that cAMP contributes to the activation of ischemically sensitive abdominal visceral afferents. Single-unit activity of abdominal 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 responses 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 cyclase, 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 impulses/s (P < 0.05; n = 8). Furthermore, whereas exogenous PGE(2) (3-4 microg/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 augmented 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, demonstrated similar increases in the activity of afferents with repeated administration of PGE(2). These data suggest that cAMP contributes to the activation of abdominal visceral afferents during ischemia, particularly to the action of PGs on activation and/or sensitization of these endings.
Guo
Z L
ZL
Department of Medicine, University of California, Irvine, California 92697, USA. zguo@uci.edu
Longhurst
J C
JC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000005:Abdomen / Q000098:blood supply* / Q000294:innervation*; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D000344:Afferent Pathways / Q000503:physiopathology*; D000818:Animals; D002415:Cats; D000242:Cyclic AMP / Q000502:physiology*; D016048:Dideoxyadenosine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016048:Dideoxyadenosine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015232:Dinoprostone