Receptors for angiotensin: a critical analysis

Abstract

Angiotensin exerts numerous contractile and secretory effects by activating specific receptors. Recent pharmacological findings obtained with this peptide in various laboratories are analyzed, using the order of potency of agonists and the affinity of competitive antagonists as criteria for the classification of receptors for angiotensin in several systems. The analysis is restricted to experiments in which biological effects have been measured. Desensitization (the third criterion for classification of receptors) is discussed and a new protocol is proposed for its utilization. The analysis reveals that receptors for angiotensin in intestinal and vascular smooth muscles, in the heart, and in the vas deferens are all of the same type, while the receptors mediating the release of catecholamines from the adrenal medulla and those subserving the steroidogenic action on the adrenal cortex remain still unidentified. The recently proposed role of ATI as mediator of renin in the adrenal medulla is not substantiated by pharmacological findings with decapeptide antagonists. Moreover, the utilization of ATI as an agonist to determine the order of potency of angiotensins and the use of SQ 20881 as an inhibitor of the converting enzyme have shown serious limitations and should be reconsidered. The hypothetical role of ATIII as mediator of the renin-angiotensin system in the adrenal cortex, at least in other species than the rat, appears to be supported by the high affinity of heptapeptide antagonists for the adrenocortical receptor. However, these antagonists have generally been compared with [Sar1,Ala8]-ATII, A compound which is definitely inadequate for evaluating the affinities of octapeptides in the adrenal cortex. Therefore most of the data supporting the role of ATIII in this system have to be carefully reconsidered. Analogues of ATII are proposed for using as agonists and as antagonists instead of the natural angiotensins (for determining the order of potency of agonists) and instead of [Sar1,Ala8]-ATII (for measuring the affinities of competitive antagonists).