Sa1956 Stable Gastric Pentadecapeptide BPC 157 Protects Against Pertinent Ischemic Challenge (Left Gastric Artery Ligation) in Rats
Aim. We focused on poorly studied effect of haloperidol (H) on lower esophageal and pyloric sphincter pressure, NO-synthase (NOS) blockade by L-NAME, and counteracting effect of stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419), already successfully tested in patients with inflammatory bowel disease. Haloperidol, useful for severe nausea/emesis by acting at the chemoreceptor trigger zone (CTZ), is also ulcerogen, both producing and aggravating gastric lesions (Life Sci, 2001;68:1905-12). BPC 157 antagonizes haloperidol catalepsy and gastric lesions (Eur J Pharmacol, 1999;379:19-31), and has a particular anti-reflux effect on sphincters in health and diseased animals (J Pharm Sci, 2006; 102:269-77; 2007; 104:7-18). Methods. In all rats LES and PS pressure manometrical evaluation (cmH2O) was as described (J Pharm Sci, 2006; 102:269-77; 2007; 104:7-18) (the values of 68-76 cmH2O for LES and 68-74 cmH2O for PS as normal as determined before). Medication was haloperidol (6.25, 12.5, 25mg/kg/day ip) (given in ulcerogenic doses), BPC 157 (10ug, 10ng/kg/day ip) for 7 days, last application 30 min before assessment, L-NAME (5mg/kg ip) at 30min before assessment. Results. Haloperidol consistently produced a fall in LES (65±1 (H 6.25); 66±1 (H 12.5), 64±1 (H 25) and an even more prominent drop in PS (55±2;56±1;54±2 (H 6.25; 12.5; 25)); L-NAME co-administration induced an aggravation (LES below 60; PS below 50 cmH2O). Contrary, BPC 157 both doses counteracted haloperidol-induced fall in sphincters pressure, with a marked increase (PS) or even a rise till the normal values (LES). Likewise, BPC 157, given with L-NAME, counteracted L-NAME-aggravation of haloperidol-induced fall in sphincters pressure. Conclusions. Haloperidol-induced fall in sphincters pressure that contributes to its ulcerogenic effect is NOsystem related, while BPC 157 maintains and rescues LES and PS-function.