Receptors for angiotensin: A critical analysis

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Abstract
Angiotensin exerts numerous contractile and secretory effects by activating specific receptors. Recent pharmacological findings obtained with this peptide in various laboratories were 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 was restricted to experiments in which biological effects were measured. Desensitization (the 3rd criterion for classification of receptors) was discussed and a new protocol was proposed for its utilization. The analysis revealed 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 [angiotensin I] as mediator of renin in the adrenal medulla was not substantiated by pharmacological findings with decapeptide antagonists. The utilization of ATI as an agonist to determine the order of potency of angiotensins and the use of SQ 20881 [tepnotide] as an inhibitor of the converting enzyme have shown serious limitations and should be reconsidered. The hypothetical role of ATIII [angiotensin III] as mediator of the renin-angiotensin system in the adrenal cortex, at least in other species than the rat, appeared to be supported by the high affinity of heptapeptide antagonists for the adrenocortical receptor. 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. Analogs of ATII [angiotensin II] were 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).

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