Central Metabolism of Angiotensins: Potential Functional Significance

Abstract

Many species^2/7 have both pressor and dipsogenic responses to intracerebroventricularly (ICV) applied angiotensin II (AII) and III (AIII). Implicit in this central nervous system (CNS) responsiveness to AII and AIII is the existence of specific membrane-bound receptors. Furthermore these receptors would be expected to be present in those areas of the CNS which are known to be angiotensin sensitive, namely the circumventricular organs⁴. Surprisingly, this logical inference with regard to the distribution of receptors as determined by radioligand binding methods has not been consistently validated when ¹²⁵I-AII is used as the labeled ligand in the presence of chelating agents^1/3/6. However, when ¹²⁵I-AIII is used as the radioligand, “apparent” binding is seen in many brain regions in every species examined. The term “apparent” is used because high performance liquid Chromatographic (HPLC) analysis of bound label derived from ¹²⁵I-AIII incubated membranes clearly indicated that degradation products, especially ¹²⁵I-tyrosine (Tyr), make up the large majority of bound label. This finding, may, in fact, indicate that “apparent” AIII binding is artifactual in the sense that it has nothing to do with angiotensin binding sites but may represent nonspecific degradation of angiotensins and subsequent uptake of labeled products. On the other hand, this degradation and tyrosine transloction may be a concerted event that accompanies angiotensin binding, suggesting that specific peptidases may be a part of the receptor complex. This study which examines these possibilities strongly supports this notion.