Recombinant interleukin-1β inhibits gastric acid secretion by activation of central sympatho-adrenomedullary outflow in rats

• Published in: European journal of pharmacology 1995-06, Vol.279 (2), p.233-239
• Main Authors: Yokotani, Kunihiko, Okuma, Yasunobu, Osumi, Yoshitsugu
• Format: Article
• Language: English
• Subjects: Adrenal Medulla - drug effects; Adrenal Medulla - physiology; Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Anesthesia; Animals; Biological and medical sciences; Depression, Chemical; Dose-Response Relationship, Drug; Electric Stimulation; Fundamental and applied biological sciences. Psychology; Gastric Acid - metabolism; Gastric acid secretion; Humans; Indomethacin; Injections, Intraventricular; Interleukin-1 - administration & dosage; Interleukin-1 - pharmacology; Interleukin-1β; Male; Phentolamine - pharmacology; Propranolol - pharmacology; Rats; Rats, Wistar; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacology; Stomach; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology; Sympatho-adrenomedullary system; Urethane; Vagus Nerve - physiology; Vertebrates: digestive system; α-Adrenoceptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00166-I

The inhibitory mechanism of gastric acid secretion induced by human recombinant interleukin-1β was investigated in bilaterally vagotomized, urethane-anesthetized rats. Intracerebroventricular administration of interleukin-1β (10, 50 and 100 ng/animal) dose dependently inhibited the gastric acid secretion induced by electrical stimulation of the vagus nerve at 3 Hz. Inhibition of gastric acid secretion induced by interleukin-1β (50 ng/animal) was abolished both by splanchnectomy and by phentolamine (5 mg/kg i.m.). Greater splanchnic nerves ramify into the adrenal branch and gastric sympathetic preganglionic branch. The interleukin-1β (50 ng/animal)-induced inhibition was also abolished by intracerebroventricular pretreatment with indomethacin (500 μg/animal), while pretreatment with the same dose of this reagent by the intraperitoneal route was without effect. These results suggest that centrally administered interleukin-1β induces a prostaglandin-mediated central excitation of the sympatho-adrenomedullary system, and the resultant activation of gastric α-adrenoceptors inhibits the vagally stimulated gastric acid secretion in rats.