Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9-39).
Glicentin and glucagon-like peptide-1 (7-36) amide (GLP-1) are gut hormones released during digestion. Glicentin and GLP-1 slow down gastric emptying and glicentin can switch off the duodenojejunal fed motor pattern. The effect of glicentin on the motor activity of colon has never been reported in humans. Our aim was to determine if circular smooth muscle cells (SMC) from the human colon are target cells for glicentin or GLP-1, and if their motility is dependent upon these digestive hormones.


METHODS
Twenty-two resections were performed on patients operated for colon adenocarcinoma. The SMC were isolated from colonic circular muscle layer and cell contraction was assessed.


RESULTS
Glicentin caused a dose-related contraction of SMC, when GLP-1 determined a contraction of weak amplitude. Exendin-(9-39), described as a GLP-1 receptor antagonist, inhibited contraction due to glicentin or GLP-1. In contrast, on antral SMC from rabbit, GLP-1 exerts neither relaxation nor contraction; however, exendin-(9-39) dose dependently reduced the contractile activity of glicentin [glicentin EC(50) = 5 pM, exendin-(9-39) pA(2) = -9.36].


CONCLUSIONS
The circular muscle from the human colon is a target tissue for glicentin and GLP-1. Whereas glicentin is a long-life digestive hormone which would contribute to segmental contraction, the biological activity of GLP-1 remains unknown on this tissue. On the digestive smooth muscle, exendin-(9-39) behaved as an antagonist for two members of the glucagon-receptor family, GLP-1 and glicentin.
Ayachi
S E
SE
Laboratory of Signalling of Normal and Tumoral Cells, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier cedex 05, France.
Borie
F
F
Magous
R
R
Sasaki
K
K
le Nguyen
D
D
Bali
J-P
JP
Millat
B
B
Jarrousse
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D053771:Glicentin; D005934:Glucagon / Q000235:genetics / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011498:Protein Precursors / Q000235:genetics / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D010446:Peptide Fragments; D011498:Protein Precursors; C083773:exendin (9-39); D004763:Glucagon-Like Peptides; D053771:Glicentin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon