Potencies of various neurotensin-(8–13) analogs for inhibition of heat-induced edema in the anesthetized rat

Abstract

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°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 Tyr 11 with Trp in NT-(8–13) and Arg 8 with d-Arg resulted in an analog [ d-Arg 8, Trp 11]NT-(8–13) which was 5-times more potent than NT-(8–13). Substitution of d-Arg for Arg 8 and Arg 9 in NT-(8–13) produced analogs that retained anti-edema activity but with decreased effects on gut motility and hypotension.