Potencies of various neurotensin-(8-13) analogs for inhibition of heat-induced edema in the anesthetized rat.
Peptides of the neurotensin (NT) and xenopsin (XP) families inhibit vascular leakage in various models of tissue injury. In this study, we measured the potency of NT fragments, NT analogs and NT-(8-13) analogs for inhibition of thermal edema induced by immersion of the anesthetized rat's paw in 58 degrees C water for 1 min. The pattern of anti-edema potencies seen with sixteen NT-(8-13) analogs correlated well with the pattern of activities obtained in binding measurements to rat brain membrane preparations and to activities in isolated organ preparations. Replacement of Tyr11 with Trp in NT-(8-13) and Arg8 with D-Arg resulted in an analog [D-Arg8, Trp11]NT-(8-13) which was 5-times more potent than NT-(8-13). Substitution of D-Arg for Arg8 and Arg9 in NT-(8-13) produced analogs that retained anti-edema activity but with decreased effects on gut motility and hypotension.
Gao
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School of Public Health, University of California, Berkeley 94720-7360, USA.
Wei
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D000595:Amino Acid Sequence; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004487:Edema / Q000209:etiology* / Q000517:prevention & control*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006358:Hot Temperature / Q000009:adverse effects*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides; D051381:Rats; D017207:Rats, Sprague-Dawley; D029867:Xenopus Proteins
D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D029867:Xenopus Proteins; D009496:Neurotensin; C016832:xenopsin; C054381:neurotensin (8-13)