THE ANGIOTENSIN-IV SYSTEM - FUNCTIONAL IMPLICATIONS

The brain renin-angiotensin system has been implicated in the central regulation of the cardiovascular system, body water balance, and cycli c regulation of reproductive hormones and behaviors. It also exerts so me influence over the secretion of pituitary hormones. This system app ears to be complete with the necessary precursors and enzymes for the formation and degradation of biologically active forms of angiotensins and several binding subtypes that are presumed to mediate these and o ther functions. Much information is now available on the AT(1) site wh ich preferentially binds angiotensin II (AngII), but also binds angiot ensin III (AngIII), and appears to be responsible for mediating the ab ove described classic angiotensin physiologies and behaviors. Less is known about the functional importance of the ATE site which also binds AngII but preferentially binds AngIII. This site has been implicated in vascular growth and cerebral blood flow. Recently, an AT(4) site ha s been discovered and characterized that preferentially binds AngII (3 -8), a fragment of AngII referred to as angiotensin IV (AngIV). This A T(4) site is prominent in cerebral cortex, hippocampus, basal ganglia, cerebellum, and spinal cord, as well as several peripheral tissues in cluding kidney, bladder, heart, spleen, prostate, adrenals, and colon. The AT(4) site may mediate memory acquisition and recall and the regu lation of blood flow. The function(s) of the AT(4) receptor subtype in peripheral tissues is currently unknown, although it does appear to b e involved in kidney blood flow. (C) 1995 Academic Press, Inc.