EXPRESSION OF ANGIOTENSIN TYPE-1 (AT1) AND TYPE-2 (AT2) RECEPTOR MESSENGER-RNAS IN THE ADULT-RAT BRAIN - A FUNCTIONAL NEUROANATOMICAL REVIEW

The discovery that all components of the renin-angiotensin system (RAS ) are present in the central nervous system led investigators to postu late the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurons have been visualized in the brain. Two major pa thways were described: a forebrain pathway which connects circumventri cular organs to the median preoptic nucleus, paraventricular nucleus, and supraoptic nucleus, and a second pathway connecting the hypothalam us to the medulla oblongata. Blood-brain barrier deficient circumventr icular organs are rich in angiotensin II receptors. By activating thes e receptors, circulating angiotensin II may act on central cardiovascu lar centers via angiotensinergic neurons, providing a link between per ipheral and central angiotensin II systems. Among the effector peptide s of the brain RAS, angiotensin II and angiotensin III have the same a ffinity for the two pharmacologically well-defined receptors: type 1 ( AT1) and type 2 (AT2). When injected in the brain, these peptides incr ease blood pressure, water intake, and anterior and posterior pituitar y hormone release and may modify memory and learning. The cloning of A T1 and AT2 receptor cDNAs has revealed that these receptors belong to the seven transmembrane domain receptor family. In rodents, two AT1 re ceptor subtypes, AT1A and AT1B, have been isolated. Using specific rib oprobes for in situ hybridization histochemistry, recent studies mappe d the distribution of AT1A, AT1B, and AT2 receptor mRNAs in the adult rat and found a predominant expression of AT1A and AT2 mRNA in the bra in and of AT1B in the pituitary. Very limited overlap was found betwee n the brain expression of AT1A and AT2 mRNAs. In several functional en tities of the brain, such as the preoptic region, the hypothalamus, th e olivocerebellary system, and the brainstem baroreflex are, the coloc alization of receptor mRNA, binding sites, and angiotensin immunoreact ive nerve terminals suggests local synthesis and expression of angiote nsin II receptors. In other areas, such as the bed nucleus of the stri a terminalis, the median eminence, or certain parts of the nucleus of the solitary tract, angiotensin II receptors are likely of extrinsic o rigin. The neuronal expression of AT1A and AT2 receptors was demonstra ted in the subfornical organ, the hypothalamus, and the lateral septum . By using double label in situ hybridization, AT1A receptor expressio n was localized in corticotropin releasing hormone but not in vasopres sin containing neurons in the hypothalamus. The information is discuss ed together with functional data concerning the role of brain angioten sins, in an attempt to provide a better understanding of the physiolog ical and functional roles of each receptor subtype. (C) 1997 Academic Press.