Differential effect of 5- and 15-lipoxygenase products on ischemically sensitive abdominal visceral afferents.
The effects of 5- and 15-lipoxygenase products, leukotriene B4 (LTB4) and (8R,15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on ischemically sensitive abdominal visceral C fiber afferents were evaluated, because this system is important in sensitizing cutaneous afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of ischemia. Inhibition of 5-lipoxygenase with WY-50295 tromethamine (5 mg/kg iv) augmented the impulse activity from 0.48 +/- 0.15 to 0.79 +/- 0.24 impulses/s (P < 0.05) in seven ischemically sensitive afferents. Conversely, topical application of LTB4 (125 ng) directly onto the receptive field attenuated impulse activity of 10 ischemically sensitive C fiber afferents from 0.82 +/- 0.23 to 0.42 +/- 0.10 impulses/s (P < 0.05). In additional cats, application of 8R,15S-diHETE (125 ng) onto the receptive field augmented the impulse activity of nine ischemically sensitive C fiber afferents (from 0.48 +/- 0.15 to 0.70 +/- 0.15 impulses/s, P < 0.05) and significantly decreased the mechanical threshold of these nine afferents, whereas application of 8S,15S-diHETE (125 ng), a stereoisomer of 8R,15S-diHETE, attenuated the impulse activity from 0.77 +/- 0.48 to 0.45 +/- 0.13 impulses/s (P < 0.05) in six additional ischemically sensitive C fiber afferents. In animals pretreated with aspirin (50 mg/kg iv, n = 6) or 8S,15S-diHETE (125 ng, n = 6), WY-50295 tromethamine (5 mg/kg iv) still potentiated the impulse activity of ischemically sensitive C fiber afferents. These data indicate that 8R,15S-diHETE interacts with stereospecific receptors to sensitize, whereas LTB4 reduces, the response of abdominal visceral afferents to ischemia. Furthermore the data suggest that the augmented response of afferents to abdominal ischemia after inhibition of 5-lipoxygenase is, at least in part, independent of shunting to the cyclooxygenase or 15-lipoxygenase system.
Pan
H L
HL
Department of Internal Medicine, University of California, Davis 95616, USA.
Stahl
G L
GL
Longhurst
J C
JC
D000005:Abdomen; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002415:Cats; D004594:Electrophysiology; D007511:Ischemia / Q000503:physiopathology*; D007975:Leukotriene B4 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D009280:Naphthaleneacetic Acids / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology; D014781:Viscera / Q000098:blood supply* / Q000294:innervation*
D009280:Naphthaleneacetic Acids; D011804:Quinolines; C067525:S(alpha)-methyl-6-(2-quinolinylmethoxy)-2-naphthaleneacetic acid; D007975:Leukotriene B4; C030722:8,15-leukotriene B4; D008084:Lipoxygenase; D001241:Aspirin