Regulation of the brain angiotensin system: a thesis of multicellular involvement

Many potential sites of regulation may be envisioned for the brain angiotensin system. However, new findings indicate that regulatory mechanisms may be more complex and detailed then previously recognized. These results, summarized below, include the recent findings of probable glial involvement in the brain angiotensin system, the potential for neuronal-glial interaction and the role of peptidases in either the activation of the relevant angiotensin peptide or in the termination of action of angiotensin II. A hypothesis is presented which proposes that a subpopulation of glia function to convert angiotensin II to angiotensin III so as to facilitate the rapid inactivation of the octapeptide. This could be a mechanism both for terminating action of the peptide at a neuronal receptor as well as for shielding receptors from exogenous angiotensins. Glia may also scavenge angiotensinogen from extracellular fluids, thereby limiting the lifetime of the prohormone. Thus, cross-talk between glia and neurons is proposed as one element of regulation of the brain angiotensin system.