Role of endogenous serotonin and histamine in the pathogenesis of gastric mucosal lesions in unanaesthetised rats with a single treatment of compound 48/80, a mast cell degranulator.
In unanaethetised rats with a single injection of compound 48/80, a mast cell degranulator (0.75 mg kg-1, i.p.), gastric lesions occurred with increased serum serotonin and histamine levels and reduced gastric mucosal blood flow at 0.5 h after the injection and developed at 3 h. Pretreatment with either cyproheptadine (a serotonin and histamine antagonist) or methysergide (a serotonin antagonist) prevented the formation of gastric mucosal lesions with attenuation of reduced gastric mucosal blood flow at 0.5 h after compound 48/80 injection, while pretreatment with either amitriptyline (a selective inhibitor of histamine release from mast cells), tripelennamine (a histamine H1-receptor antagonist), famotidine (a histamine H2-receptor antagonist) or cimetidine (a histamine H2-receptor antagonist) had no effect. Pretreatment with either cyproheptadine, methysergide, amitriptyline or tripelennamine prevented the development of gastric mucosal lesions at 3 h after compound 48/80 injection, while pretreatment with either famotidine or cimetidine had no effect. These results indicate that in unanaesthetised rats with a single compound 48/80 treatment, acutely released endogenous serotonin causes gastric mucosal lesions, while released endogenous histamine mainly contributes to the lesion development and that gastric acid plays little role in the pathogenesis of the compound 48/80-induced acute gastric lesions.
Ohta
Y
Y
Department of Biochemistry, School of Medicine, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
Kobayashi
T
T
Ishiguro
I
I
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000639:Amitriptyline / Q000627:therapeutic use; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D002927:Cimetidine / Q000627:therapeutic use; D003533:Cyproheptadine / Q000627:therapeutic use; D015738:Famotidine / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D006632:Histamine / Q000097:blood / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008784:Methysergide / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000097:blood* / Q000139:chemically induced* / Q000517:prevention & control; D014309:Tripelennamine / Q000627:therapeutic use; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
D018759:Adrenergic Uptake Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D012702:Serotonin Antagonists; D000639:Amitriptyline; D003533:Cyproheptadine; D012701:Serotonin; D014309:Tripelennamine; D003189:p-Methoxy-N-methylphenethylamine; D015738:Famotidine; D002927:Cimetidine; D006632:Histamine; D008784:Methysergide