Arachidonic acid cascade and stimulation of acetylcholine release by human recombinant interleukin-1 beta in guinea pig ileum.
We examined the effect of interleukin 1 beta (IL-1 beta) on enteric cholinergic neuronal activity in the isolated guinea pig ileum. Pretreatment with human recombinant IL-1 (hr IL-1) (100-1000 pg/ml) for 15 to 60 min potentiated contractions of the ileum induced by electrical transmural stimulation (ETS) (1 Hz, 1 msec, for 1 min) in a time- and concentration-dependent manner, hrIL-1 beta (300-1000 pg/ml) potentiated the ETS- (1 Hz, 1 msec, for 2 min) evoked release of [3H]acetylcholine (ACh) from entire preparations of ileum preloaded with [3H]choline, but not from longitudinal-myenteric plexus preparations and mucosa-free preparations, in a time- and concentration-dependent manner. The maximum effect of IL-1 beta on both responses was obtained 60 min after exposure to 1000 pg/ml IL-1 beta. hrIL-1 alpha had no effect on the contractions and [3H]ACh release induced by ETS. The boiled hrIL-1 beta and the hrIL-1 beta absorbed with anti-hrIL-1 beta antibody failed to potentiate the ETS-evoked release of [3H]ACh. Cycloheximide (100 micrograms/ml), mepacrine (10(-6) M), indomethacin (3 x 10(-6) M) and nordihydroguaiaretic acid (10(-5) M) inhibited the potentiating effect of IL-1 beta, with no effect on the ETS-evoked release. Thus, IL-1 beta stimulates enteric cholinergic neurons through the arachidonic acid cascade produced in tissues other than longitudinal muscle and myenteric plexus of the guinea pig ileum.
Mameya
S
S
Department of Pharmacology II, Nagasaki University School of Medicine, Japan.
Sawa
T
T
Taniyama
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical; D013373:Substance P / Q000502:physiology
D007375:Interleukin-1; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D016718:Arachidonic Acid; D009569:Nitric Oxide; D013373:Substance P; D003513:Cycloheximide; D000109:Acetylcholine