Neuromedin U acts in the central nervous system to inhibit gastric acid secretion via CRH system

Neuromedin U ( NMU) is a hypothalamic peptide involved in energy homeostasis and stress responses. NMU, when administered intracerebroventricularly, decreases food intake and body weight while increasing body temperature and heat production. In addition, NMU, acting via the corticotropin-releasing hormone (CRH) system, induces gross locomotor activity and stress responses. We studied the effect of intracerebroventricularly administered NMU (0.5-4 nmol) in the regulation of gastric functions in conscious rats. Intracerebroventricular administration of NMU significantly decreased gastric acid output to 30-60% and gastric emptying to 35-70% in a dose-dependent manner. Vagotomy did not abolish the inhibitory effect of NMU on pentagastrin-induced gastric acid secretion. Pretreatment with indomethacin ( 10 mg/kg), an inhibitor of prostaglandin synthesis, also did not affect NMU-induced acid inhibition. Pretreatment with anti-CRH IgG ( 1 mug/rat), however, completely blocked NMU-induced acid inhibition ( P < 0.01). Administration of yohimbine ( 4 mg/kg), an alpha(2)-adrenergic receptor antagonist, also abolished NMU-induced acid inhibition ( P < 0.01). These findings suggest that NMU is critical in the central regulation of gastric acid secretion via CRH.