Structure-activity studies with neurotensin: analysis of positions 9, 10 and 11.
1 The stimulant effects of neurotensin (NT) and NT analogues modified in positions 9, 10 or 11 were evaluated and compared in two pharmacological preparations: the rat stomach strip and the isolated spontaneously beating atria of guinea-pig. 2 The data derived from our structure-activity study suggest that Arg9 and Pro10 mainly contribute to the affinity of neurotensin for its cardiac and smooth muscle receptors. Tyr11 seems to be more closely involved in the process of receptor activation by NT. 3 The order of potency of some NT analogues modified in position 11 (e.g. [D-Phe11]-NT, [D-Tyr11]-NT) was strikingly different from that described in other systems (e.g. hypothermia test and specific mast cell binding). The importance of this observation is discussed.
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000187:drug effects; D013329:Structure-Activity Relationship
D009496:Neurotensin