Sarcosine1, glycine8 angiotensin II is a functional AT1 angiotensin receptor antagonist.

Sarcosine1, glycine8 angiotensin II (SG Ang II) displayed unusual characteristics in early pharmacological studies. It was a potent antagonist of the dipsogenic actions of intracerebroventricularly administered Ang II in the rat, but showed low affinity for bovine cerebellar Ang II receptors. It has recently been shown that SG Ang II binds preferentially to the AT1 receptor. To determine if SG Ang II is a functional antagonist of the AT1 receptor-mediated calcium signaling, CHO cells stably transfected with AT1 receptors were exposed to Ang II in the presence and absence of SG Ang II. At concentrations of 10-100 nM, SG Ang II completely inhibited Ang II-stimulated intracellular Ca2+ mobilization in AT1A and AT1B receptor-transfected cells. SG Ang II and 125I- SG Ang II bound to AT1A and AT1B receptor-transfected cells with KD and KI values of 2-4 nM. In contrast, SG Ang II bound to AT2 transfected cells with a KI value of 7.86 microM. These results demonstrate that SG Ang II is a selective and functional peptide antagonist of the AT1 angiotensin II receptor subtype.