Angiotensin receptive neurones in the subfornical organ. Structure-activity relations.

A microiontophoretic study was performed of the actions of angiotensin II and angiotensin fragments on neurones of the subfornical organ (SFO). Adult cats were anaesthetized and the SFO exposed for penetration by a multibarrelled micropipette. We found that angiotensin II-[2--8]-heptapeptide shows a significantly higher stimulation of firing rate compared to angiotensin II. Angiotensin II-[5--8]-tetrapeptide still produced an excitatory action on a single units. Both the action of the heptapeptide and the tetrapeptide were blocked by [sar1, Ala8]-angiotensin II (P 113). In contrast, angiotensin II-[6--8]-tripeptide failed to enhance the firing rate of the same neurones. Our data indicate that angiotensin II and some shorter chain peptide fragments can directly affect neurones of the SFO. The study may give new insight in structure-activity relations for angiotensin II. The results support the hypothesis that the subfornical organ is a receptor site which is available to this peptide.