Paiva T B, Miyamoto M E, Juliano L, Paiva A C
J Pharmacol Exp Ther. 1977 Aug;202(2):294-300.
The ability of angiotensin II (AII) and of seven N-terminally modified peptide analogs to induce tachyphylaxis in isolated preparations of the rat uterus and the guinea-pig ileum was found to correlate well with the degree of amino group protonation. No correlation was found between tachyphylaxis and the affinity for the rat uterus receptors, as measured by the reciprocals of ED50 values. Dissociation between the tachyphylactic property and receptor affinity in the rat uterus was also evident by lowering the calcium concentration in the medium, which resulted in increased tachyphylaxis without significant changes in ED50 values. In the guinea-pig ileum, tachyphylaxis correlated with the reciprocal of ED50, but there was a better correlation with amino group protonation. [6-Pyrazolylalanine] AII was approximately as tachyphylactic as AII in both smooth muscles studied, indicating that protonation of the histidine side-chain may not be important for the manifestation of tachyphylaxis. The recovery of the guinea-pig ileum for AII tachyphylaxis was not affected by repeated treatments with BaCl2, but it was partially impaired by [Suc1]AII, des-Asp-AII, bradykinin and histamine.
