Differences in transport rate of oxytocin and vasopressin analogues across proximal and distal isolated segments of the small intestine of the rat.
The transmural intestinal passage of some oxytocin and vasopressin analogues (oxytocin, OT; [Mpa1, D-Arg8]vasopressin, dDAVP; [Mpa1, Tyr (OMe)2, carba6]oxytocin, carbetocin; [Mpa1, D-Tyr (OEt)2, Thr4, Orn8]vasotocin, antocin II; [Mpa1, D-Tyr (OEt)2, Thr4, desPro7Orn8Gly9NH2]tocinoic acid-NH(CH2)3NH2, desPOG-antocin II-NH(CH2)3NH2) was studied using isolated proximal and distal segments in the rat. All peptides (measured as peptide-like immunoreactivity) displayed a higher transport rate across distal intestinal segments as determined by radioimmunoassay (RIA). The smallest peptide, des POG-antocin II-NH(CH2)3NH2, was transported at the fastest rate. No correlation of lipophilicity with transport rate was observed. Determination of the amount of peptide remaining in the mucosal media at the end of the incubation period by HPLC did not reveal any visible degradation products. However, the large difference in transport rate between [3H]OT and immunoreactive OT indicates mucosal metabolism of this peptide. [3H]d-DAVP was distributed in a larger mucosal volume than the extracellular space marker [3H]inulin, indicating tissue uptake, but was too low (less than 100% of buffer concentration) to make an active transport mechanism likely. The differences in peptide transport rates between proximal and distal intestinal segments are most likely due to a higher distal paracellular permeability despite a decreased absorptive surface area at this region.
Lundin
S
S
Department of Clinical Pharmacology, Lund University, Sweden.
Pantzar
N
N
Broeders
A
A
Ohlin
M
M
Weström
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003894:Deamino Arginine Vasopressin / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008055:Lipids; D008969:Molecular Sequence Data; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014667:Vasopressins / Q000737:chemistry / Q000493:pharmacokinetics*
D008055:Lipids; D014667:Vasopressins; D010121:Oxytocin; D003894:Deamino Arginine Vasopressin