Abstract
Histamine releasing effects of neurotensin (NT) and several NT fragments and structural analogues were measured in the rat perfused hindquarter. The results show that the chemical groups responsible for histamine release are located in the C-terminal sequence Arg 9-Pro 10-Tyr 11-Ile 12-Leu 13-OH. Both the spatial configuration and positive charge of Arg 8 and Arg 9 appear to contribute to the histamine releasing effect of NT. Optimization of the histamine releasing effect of NT requires both a free C-terminal carboxyl group and the presence in position 11 of NT of an aromatic residue, with the L-configuration, bearing an heteroatom capable of hydrogen bonding with the receptor. The results indicate that the structural requirements of NT to induce histamine release from the rat perfused hindquarter are similar to those involved in other peripheral biological actions of NT.
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