The role of sensory neurons in the antiulcer effect of centrally injected amylin in rat.
Central administration of amylin (2.2 microg/rat, i.c.v.) reduces (from a minimum of 67% to 83%) indomethacin (Indo, 20 mg Kg(-1), orally) induced ulcers in rats. The anti-ulcer effect of the peptide is not removed by the administration of prokinetic drugs like domperidone or neostigmine but it is reduced by 35% in rats treated with capsaicin or with the CGRP antagonist, CGRP(8-37). These data indicate that amylin gastroprotection involves capsaicin-sensitive nerve fiber leading to CGRP-dependent gastric vasodilatory effect. Additional mechanisms could involve noradrenergic alpha(2) receptors as the peptide gastroprotective activity is reduced from 67% to 20% by the alpha(2) antagonist yohimbine.
Guidobono
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F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, 20129, Milano, Italy. guidobon@mailserver.unimi.it
Pagani
F
F
Sibilia
V
V
Soglian
A
A
Rapetti
D
D
Netti
C
C
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000682:Amyloid; D000897:Anti-Ulcer Agents; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015016:Yohimbine; D009388:Neostigmine; D004294:Domperidone; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin