Neurotensin and neuromedin N stimulate mucin output from human goblet cells (Cl.16E) via neurotensin receptors.
The stably differentiated human intestinal goblet cell line Cl.16E was used to study the effects of two structurally related regulatory peptides, neurotensin (NT) and neuromedin N (NN), on mucus secretion. NT and NN stimulated rapid release of mucins from filter-grown Cl.16E cells, this effect being dose related with a mean effective dose of 36 nM for NT and 422 nM for NN. The order of potency of NT, three NT fragments corresponding to the NH2-terminal part [NT-(1-11)] or to the COOH-terminal part [NT-(8-13) and NT-(9-13)], and NN in promoting mucin release and in inhibiting 125I-labeled NT binding to Cl.16E cell membranes was identical with NT greater than or equal to NT-(8-13) greater than NN greater than NT-(9-13) much greater than NT-(1-11) supporting the hypothesis that NT and NN stimulate mucin output through interaction with a common NT-preferring receptor. Scatchard analysis of equilibrium binding data showed one population of NT binding sites in Cl.16E cell membranes with the following characteristics: binding capacity (Bmax) was 141 fmol/mg of protein and dissociation constant (Kd) was 1.00 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
Augeron
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Laboratoire de Biologie et de Physiologie des Cellules Digestives, U239 Institut National de la Santé et de la Recherche Médicale, Faculté Bichat, Paris, France.
Voisin
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T
Maoret
J J
JJ
Berthon
B
B
Laburthe
M
M
Laboisse
C L
CL
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism*; D009496:Neurotensin / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology*; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D009077:Mucins; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; C042090:neuromedin N; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D002217:Carbachol; D000242:Cyclic AMP; D002118:Calcium