Effects of centrally of peripherally injected adrenomedullin on reserpine-induced gastric lesions.
Adrenomedullin intracerebroventricularly administered (0.1 to 20 ng/rat i.c.v.), showed significant gastroprotective activity in a dose-dependent manner. When the peptide was intravenously administered (1 to 1000 ng/kg i.v.) it did not show significant gastroprotective activity in the same test. The gastroprotective effect of the peptide (10 ng/rat) was abolished by bilateral adrenalectomy, by pretreatment with the beta-adrenoceptor antagonist, propranolol (1 mg/kg i.p.), or by a calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) fragment (1 or 10 ng/rat i.c.v.). This study showed that adrenomedullin is protective against reserpine-induced gastric lesions, that the action involves sympathetic nerve activity, and moreover interferes with CGRP receptors.
Clementi
G
G
Institute of Pharmacology, University of Catania, School Medicine, Italy.
Caruso
A
A
Cutuli
V M
VM
de Bernardis
E
E
Prato
A
A
Mangano
N G
NG
Amico-Roxas
M
M
D000315:Adrenalectomy; D053607:Adrenomedullin; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D013565:Sympatholytics / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000897:Anti-Ulcer Agents; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D010455:Peptides; D013565:Sympatholytics; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D012110:Reserpine; D011433:Propranolol; D015740:Calcitonin Gene-Related Peptide; D010646:Phentolamine