The ulcer healing effect of protamine sulphate in rat stomach.
BACKGROUND
Protamine sulphate has been reported to stimulate nitric oxide production from blood vessels, which is a pivotal factor for gastric ulcer healing. Our preliminary study also showed that protamine sulphate potentiated the ulcer healing effect of heparin.


METHODS
Male SD rats with acetic acid-induced gastric ulcers were given protamine sulphate (40-80 mg/kg, s.c.) twice daily for 4 or 7 days. L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), an inhibitor of nitric oxide synthase (NOS), was given s.c. prior to protamine sulphate (80 mg/kg) treatment. Ulcer healing, angiogenesis, mucosal histological changes, NOS activity and growth factors were determined.


RESULTS
Protamine sulphate dose-dependently accelerated gastric ulcer healing, which was accompanied by a significant increase in angiogenesis, mucosal regeneration and constitutive NOS activity. Inhibition of gastric secretion was observed. Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha (TNF-alpha) or inducible NOS activity was also affected. L-NAME completely blocked the beneficial effects of protamine sulphate.


CONCLUSIONS
Protamine sulphate accelerates gastric ulcer healing through a mucosal nitric oxide-dependent and possibly also the EGF-and bFGF-associated pathways, which are followed by an increase of angiogenesis and mucosal regeneration. Acid inhibition contributes in part to the ulcer healing action of protamine sulphate.
Li
Y
Y
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China.
Cho
C H
CH
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006494:Heparin Antagonists / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006494:Heparin Antagonists; D011479:Protamines; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester