Effect of adrenomedullin and proadrenomedullin N-terminal 20 peptide on sugar transport in the rat intestine.
Previous studies have shown immunostaining of adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) throughout the gastrointestinal tract. Based on these data, we decided to investigate the effect of these peptides on intestinal sugar absorption using everted rings from Wistar rat intestine. PAMP increases alpha-methylglucoside (MG) uptake at concentrations ranging from 10(-12) to 10(-7) M. AM shows a dual effect inhibiting sugar absorption at low concentrations (10(-12) to 10(-11) M) and increasing MG uptake at higher concentrations (10(-8) to 10(-6) M). In all cases, the effect is phloridzin-sensitive, indicating that the peptides alter SGLT1 function without modifying the non-mediated component of absorption. The enhancing effect of 10(-8) M AM and PAMP seems to be mediated by elevation of cAMP and is accompanied by an increase on SGLT1 expression in the brush-border membrane of the enterocytes. The inhibitory effect of 10(-12) M AM could be mediated by either cAMP reduction or, more probably, by other second messenger able to inhibit sugar absorption. PKC is not involved in the action of either AM or PAMP. These results demonstrate that both peptides play a role in the regulation of the active transport of sugars in the intestine.
Fernández de Arcaya
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Departamento de Fisiología y Nutrición, Universidad de Navarra, 31080 Pamplona, Spain.
Lostao
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MP
Martínez
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Berjón
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Barber
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D053607:Adrenomedullin; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1
D008562:Membrane Glycoproteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D010455:Peptides; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D053607:Adrenomedullin; C027020:methylglucoside