The inhibitory mechanism of GLP-1, but not glucagon, on fasted gut motility is dependent on the L-arginine/nitric oxide pathway.
Effects of glucagon-like peptide-1 (GLP-1) and glucagon on fasted gut motility in conscious rats were investigated as regards dependence on nitric oxide (NO). Small bowel motility was studied by electromyography and a jugular vein catheter was implanted for administration of drugs. GLP-1 (5-40 pmol x kg(-1) x min(-1)) prolonged the cycle length and abolished phase III of the migrating myoelectric complex (MMC) (P<0.01). Low doses of GLP-1 did not affect duration, propagation velocity or calculated length of phase III. At 1 mg x kg(-1) N(omega)-nitro-L-arginine (L-NNA) blocked the GLP-1 response up to a dose of 10 pmol x kg(-1) x min(-1) (P<0.05), while higher doses were able to overcome L-NNA-induced disinhibition of the GLP-1 response (P<0.05). Similarly, L-arginine at 300 mg x kg(-1) prevented L-NNA-induced disinhibition of the GLP-1 response (P<0.05). Glucagon (200-1000 pmol x kg(-1) x min(-1)) prolonged the cycle length and abolished phase III of MMC (P<0.01) independent of NO. Again, low doses of glucagon did not affect duration, propagation velocity or calculated length of phase III. In conclusion, inhibition of fasted motility by GLP-1 at low doses is dependent on NO, while high doses of GLP-1 and glucagon exert effects on motility independently from NO.
Tolessa
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Department of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Näslund
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Hellström
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PM
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism* / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011498:Protein Precursors; D019335:Nitroarginine; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D001120:Arginine