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Arachidonic acid cascade and stimulation of acetylcholine release by human recombinant interleukin-1 beta in guinea pig ileum

S Mameya, T Sawa and K Taniyama

Department of Pharmacology II, Nagasaki University School of Medicine, Japan.

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.

Volume 275, Issue 1, pp. 319-324, 10/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics.