Cellular uptake of a radiolabelled analogue of neurotensin in the Caco-2 cell model.
Neurotensin is a linear tridecapeptide that elicits a variety of physiological responses in the brain, including hypothermia and antinociception, and reduced levels have been linked to schizophrenia. Previously in our laboratory we developed a truncated neurotensin derivative, KK13. This hexapeptide exhibited key pharmacokinetic and behavioural characteristics of an antipsychotic and elicited central effects after oral administration. To examine the potential mechanism(s) of uptake, a radioactive analogue of KK13 (*KK13) was synthesized, characterized, and evaluated in the Caco-2 cell model of the human intestinal epithelium. Results suggested that uptake of *KK13 was a time-dependent passive process. A general linear trend in uptake was demonstrated over the concentration range (10 microM-1 m M) tested, and uptake was neither pH- nor sodium-dependent. Finally, after 60 min, intact *KK13 was identified associated with the cell components, providing further evidence for uptake and stability of the peptide.
Hadden
M Kyle
MK
Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun Street, Charleston, South Carolina 29425, USA.
Walle
Thomas
T
Dix
Thomas A
TA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors
D002250:Carbon Radioisotopes; C502329:KK13 peptide; D009842:Oligopeptides; D010446:Peptide Fragments; D009496:Neurotensin; D000255:Adenosine Triphosphate; D012964:Sodium