Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor.
OBJECTIVE
Interleukin 1 beta (IL-1 beta) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1 beta on gastric emptying were investigated.


METHODS
The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1 beta in conscious rats.


RESULTS
IL-1 beta injected intracisternally (0.01-1 ng) or intravenously (0.01-10 ng) dose-dependently decreased gastric emptying by 10%-82% and 0%-89%, respectively. The median effective dose (ED50) was 30-fold lower when IL-1 beta was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1 beta had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1 beta (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe12, [DPhe12,Nle21,38,C alpha MeLeu37]CRF12-41 (20 micrograms) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1 beta (0.1 ng). The antagonists alone had no effect on basal gastric emptying.


CONCLUSIONS
IL-1 beta acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1 beta action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.
Sütö
G
G
Center for Ulcer Research, Veterans Administration Wadsworth Medical Center, Los Angeles, California.
Király
A
A
Taché
Y
Y
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects*; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins
C083591:H-R corticotropin-releasing factor (12-41), Phe(12)-Nle(21,38), C(alpha-MeLeu(37))-; D007375:Interleukin-1; D010446:Peptide Fragments; D011453:Prostaglandins; D018019:Receptors, Corticotropin-Releasing Hormone; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; C113202:phenylalanyl corticotropin-releasing factor (12-41); D003346:Corticotropin-Releasing Hormone