Abstract
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.
MeSH terms
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Adrenalectomy
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Adrenomedullin
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Animals
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Anti-Ulcer Agents / administration & dosage
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Anti-Ulcer Agents / pharmacology
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Anti-Ulcer Agents / therapeutic use
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Calcitonin Gene-Related Peptide / pharmacology
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Calcitonin Gene-Related Peptide Receptor Antagonists
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Dose-Response Relationship, Drug
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Drug Administration Routes
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Gastric Mucosa / drug effects*
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Gastric Mucosa / pathology
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Injections, Intravenous
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Injections, Intraventricular
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Male
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Peptide Fragments / pharmacology
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Peptides / administration & dosage
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Peptides / pharmacology*
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Peptides / therapeutic use
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Phentolamine / pharmacology
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Propranolol / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reserpine / adverse effects*
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Stomach Ulcer / chemically induced
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Stomach Ulcer / prevention & control*
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Sympatholytics / pharmacology
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Vasodilator Agents / administration & dosage
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Vasodilator Agents / pharmacology*
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Vasodilator Agents / therapeutic use
Substances
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Anti-Ulcer Agents
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Calcitonin Gene-Related Peptide Receptor Antagonists
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Peptide Fragments
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Peptides
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Sympatholytics
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Vasodilator Agents
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calcitonin gene-related peptide (8-37)
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Adrenomedullin
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Reserpine
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Propranolol
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Calcitonin Gene-Related Peptide
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Phentolamine