STRUCTURE‐ACTIVITY STUDIES WITH NEUROTENSIN: ANALYSIS OF POSITIONS 9, 10 and 11

Abstract

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.