| Abstract | In this study, we compared the effects of interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) on in vitro rat gastric fundus motility. IL-1 beta and TNF produced rapid, concentration-dependent relaxation of the rat gastric fundus strips with maximal effect at 300 pg ml-1 and 10 ng ml-1, and estimated EC50S at 10 and 450 pg ml-1, respectively. The relaxant effects of IL-1 beta and TNF were not influenced by the inhibition of cyclo-oxygenase or NO-synthase activities. IL-1 beta- and TNF-induced gastric relaxations were inhibited by BW 755c, which inhibits both cyclo-oxygenase and lipoxygenase (LO), BW A4c, which selectively inhibits the 5-LO pathway, and SC 41930, a selective leukotriene B4 (LTB4) receptor antagonist, providing pharmacological evidence that LTB4 is involved in the relaxant effects of both cytokines. The IL-1 beta- and TNF-induced activation of 5-LO pathway did not appear to be triggered by phospholipase A2. An alternative pathway could involve the activation of a phospholipase C, specific for phosphatidylcholine, from which, in sequence: the formation of diacylglycerol (DAG), DAG-induced activation of protein kinase C and the formation of free arachidonic acid from DAG would ensue. This mechanism is suggested by the finding that LTB4 is able to mimic cytokine-induced strip relaxation only in the presence of phorbol 12-myristate 13-acetate, which selectively activates protein kinase C. |
| Authors | P Montuschi, G Tringali, L Parente, P Preziosi, P Navarra
(Affiliation: Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.)
|
| Journal | Pharmacological research : the official journal of the Italian Pharmacological Society
(Pharmacol Res)
Vol. 30
Issue 1
Pg. 25-33
(Jul 1994)
ISSN: 1043-6618 ENGLAND |
| PMID | 7831192
(Publication Type: In Vitro, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Interleukin-1
- Leukotrienes
- Tumor Necrosis Factor-alpha
- 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
- Type C Phospholipases
|
| Topics |
- 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
(pharmacology)
- Animals
- Dose-Response Relationship, Drug
- Female
- Gastric Fundus
(physiology)
- Gastrointestinal Motility
(drug effects)
- Interleukin-1
(pharmacology)
- Leukotrienes
(physiology)
- Male
- Rats
- Rats, Wistar
- Tumor Necrosis Factor-alpha
(pharmacology)
- Type C Phospholipases
(physiology)
|
