Angiotensin II receptors on human platelets

Abstract

The investigation of the interaction between angiotensin II and its receptors in human subjects has been hampered by the inaccessibility of human tissue containing angiotensin II receptors. In order to find a more accessible angiotensin II-binding tissue, we studied angiotensin II bindings to platelets in normal human volunteers. Platelet preparations purified on Ficoll: Isopaque gradients were incubated with 125I-angiotensin II (30 pM), with and without unlabeled angiotensin at 22° C, separating bound from free hormone by microcentrifugation. Binding was linearly related to the number of platelets incubated, and, at 8x105 cells/μl/ specific binding ranged from 0.8 to 10%. Scatchard analysis indicated a binding site with a K(D) of 2.4±0.3x10-10 M which agreed well with the K(D) by displacement analysis (3.1 x 10-10 M). The relative binding potencies for angiotensin II and analogues were: angiotensin II = des-Asp1 angiotensin II > [Sar1, Ala8] angiotensin II > des-Asp1-[Ile8] angiotensin II > angiotensin I. The effect of high and low sodium (Na) intake (200 vs. 10 mEq/day) on platelet angiotensin II binding was studied in nine subjects. Compared to low Na, high Na intake produced an 80% increase in the angiotensin II-binding capacity (P<0.01) with no significant change in binding affinity. We conclude that human platelets possess angiotensin receptors whose binding characteristics and modulation by dietary sodium resemble the properties of the receptors on 'classical' animal angiotensin target tissues. The platelet may provide an accessible source of angiotensin receptors for a detailed study of angiotensin-receptor interaction in human tissue.