Abstract
We found a potent hyperglycemic effect of proadrenomedullin N-terminal 20 peptide (PAMP) after intra-third cerebroventricular administration at a dose of 10 nmol in fasted mice. PAMP has four homologous residues with bombesin (BN), a hyperglycemic peptide. PAMP showed affinity for gastrin-releasing peptide preferring receptor (GRP-R) and neuromedin B preferring receptor. The PAMP-induced hyperglycemic effect was inhibited by [D-Phe(6), Leu-NHEt(13), des-Met(14)]-BN (6-14), GRP-R specific antagonist, indicating that the hyperglycemic effect is mediated at least in part via GRP-R. Furthermore, pretreatment of alpha-adrenergic blocker inhibited the PAMP-induced hyperglycemia and hyperglucagonemia, suggesting that the increase of glucagon secretion through alpha-adrenergic activation is involved in this hyperglycemic effect of PAMP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adrenergic alpha-Antagonists / pharmacology
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Adrenomedullin
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Animals
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Binding, Competitive
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Blood Glucose / drug effects*
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Bombesin / analogs & derivatives
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Bombesin / pharmacology
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Brain / metabolism
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Cell Line
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Cholesterol / blood
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Dose-Response Relationship, Drug
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Fatty Acids, Nonesterified / blood
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Injections, Intraventricular
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Insulin / blood
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Male
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Membranes / metabolism
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Mice
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Peptides*
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Phentolamine / pharmacology
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Proteins / metabolism
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Proteins / pharmacology*
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Radioligand Assay
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Rats
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Receptors, Bombesin / antagonists & inhibitors
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Receptors, Bombesin / genetics
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Receptors, Bombesin / metabolism*
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Triglycerides / blood
Substances
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Adrenergic alpha-Antagonists
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Blood Glucose
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Fatty Acids, Nonesterified
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Insulin
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Peptide Fragments
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Peptides
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Proteins
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Receptors, Bombesin
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Triglycerides
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Adrenomedullin
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Cholesterol
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Bombesin
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Phentolamine