Modulation of heme oxygenase/carbon monoxide system affects the inhibitory neurotransmission involved in gastrointestinal motility of streptozotocin‐treated diabetic rats

• Published in: Neurogastroenterology and motility Vol. 20; no. 11; pp. 1251 - 1262
• Main Authors: Piepoli, A. L., De Salvatore, G., Lemoli, M., De Benedictis, L., Mitolo‐chieppa, D., De Salvia, M. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2008
• Subjects: Animals; Blotting, Western; Carbon Monoxide - metabolism; diabetes; Diabetes Complications - physiopathology; Diabetes Mellitus, Experimental - physiopathology; Electric Stimulation; Enzyme Inhibitors - pharmacology; Gastrointestinal Motility - drug effects; Gastrointestinal Motility - physiology; heme oxygenase; Heme Oxygenase (Decyclizing) - metabolism; Immunohistochemistry; Male; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; neurotransmission; Organ Culture Techniques; rat duodenum; Rats; Rats, Wistar; streptozotocin; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/j.1365-2982.2008.01193.x

Alterations in gastrointestinal motility of diabetic patients have been linked to degenerative changes induced by glucose abnormalities in the peripheral nervous system. The heme oxygenase/carbon monoxide (HO/CO) signalling represents one of the non‐adrenergic/non‐cholinergic (NANC) neurotransmission pathways involved in regulation of physiological peristalsis. To investigate the role of HO/CO system in intestinal motility under diabetic conditions, the response to electrical field stimulation (EFS) and western blot analysis of HO/CO pathway components were studied on duodenum longitudinal smooth muscle strips isolated from streptozotocin (STZ)‐treated diabetic rats (65 mg kg−1, i.p.) and respective controls (CTRL), 6 weeks after the onset of diabetes. When compared to CTRL, the ability of CO releasing molecule (CORM‐3) (100–400 μmol L−1) to enhance NANC relaxation was significantly impaired in STZ‐treated rats (P < 0.05). Conversely, in vitro incubation with the HO inhibitor ZnPPIX (10 μmol L−1, 60 min) significantly reduced EFS‐induced relaxation in CTRL (P < 0.05), but not in STZ‐treated rats. Interestingly, the ability of ZnPPIX to inhibit EFS‐induced relaxation was partially restored in STZ‐treated rats co‐administered in vivo with the HO‐1 inducer cobalt protoporphyrin IX (CoPPIX) (0.5 mg per 100 g body weight weekly). Expression of inducible HO‐1 protein was increased in homogenates from STZ‐treated rats (vs CTRL, P < 0.01), and further increased in STZ‐treated rats receiving CoPPIX (P < 0.05). Taken together, our data underline the essential role of HO/CO system in regulation of inhibitory NANC neurotransmission in the duodenum and suggest that dysregulation of HO/CO activity may represent one mechanism by which gastrointestinal motility is altered in diabetes.