AJP - Regulatory, Integrative and Comparative Physiology, Vol 241, Issue 3 124-R129, Copyright © 1981 by American Physiological Society
Brain receptor binding and central actions of angiotensin analogs in rats
J. F. Mann, P. W. Schiller, E. L. Schiffrin, R. Boucher and J. Genest
The possible physiological importance of brain receptors for angiotensin
was investigated. Structure-activity relationships were established for 12
fragments and analogs of angiotensin II (ANG II). 1) Affinities of the
peptides were determined in an in vitro assay of rat brain angiotensin
receptors. 2) Blood pressure (BP) and water intake following
intracerebroventricular administration of the peptides to conscious rats
were monitored. In vitro, ANG II and [des-Asp1]ANG II displayed the highest
affinities. [Trp1]ANG II and [Trp8]ANG II had one-eighth and one-ninth the
affinity of ANG II, respectively. Multiple substitutions in positions 1, 4,
and 8 produced a 1,000-fold fall in binding affinity. Excellent correlation
was found between the in vitro binding affinities and the in vivo central
activities of the peptides on BP (r = 0.975) and on water intake (r =
0.900). The results suggest that the biochemically characterized brain
angiotensin receptors may be physiologically relevant to BP and body fluid
homeostasis. The brain angiotensin receptors mediating BP and thirst have
very similar structural requirements.
