Cysteamine induced-duodenal ulcers are associated with a selective depletion in gastric and duodenal calcitonin gene-related peptide-like immunoreactivity in rats.
We have measured the endogenous levels of gastric and duodenal calcitonin gene-related peptide (CGRP)-, neurokinin A (NKA)-, galanin-vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-like immunoreactivity (li) in relation to cysteamine-induced gastric lesions and duodenal ulcers in rats. CGRP-li but not NKA-, galanin-, VIP- or NPY-li was decreased in gastric and duodenal samples following a single ulcerogenic dose of cysteamine (900 mg/kg p.o.). Temporal relationships of this phenomenon showed that CGRP-li was selectively decreased (stomach 45%, duodenum 68% as compared to controls, respectively after 24 h) concomitantly to the formation of acute gastric lesions and duodenal ulcers. Animals bearing healed ulcers 12 days after cysteamine, had gastroduodenal CGRP-li similar to control values. Pretreatment with the selective sensory neurotoxin capsaicin decreased gastroduodenal CGRP-li but not NKA-, galanin-, VIP- or NPY-li, showing that CGRP might be considered a marker of the afferent innervation of the gastroduodenal tract. The residual gastroduodenal CGRP-li levels in capsaicin-pretreated animals were not decreased by cysteamine administration, indicating that the effect of cysteamine is restricted to a peptide pool of primary afferent origin. Duodenal CGRP-li is selectively decreased by the duodenal ulcerogen cysteamine during the acute phase of ulcers formation and might be among the local mediators which afford protection against the ulcerogenic stimuli.
Evangelista
S
S
Pharmacology Department, Malesci Pharmaceuticals, Firenze, Italy.
Renzi
D
D
Tramontana
M
M
Surrenti
C
C
Theodorsson
E
E
Maggi
C A
CA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D003543:Cysteamine / Q000008:administration & dosage / Q000009:adverse effects*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015288:Neurokinin A / Q000032:analysis; D009478:Neuropeptide Y / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000737:chemistry
D009478:Neuropeptide Y; D003543:Cysteamine; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide