Heterogeneity of Angiotensin Type 2 (AT2) Receptors
Angiotensin II (Ang II) is one of the most important hormones involved in the regulation of body fluid and cardiovascular homeostasis (1). The rate limiting step in the synthesis of Ang II is the release of the enzyme renin from the juxtaglomerular cells of the kidney into the blood. Several physiological and pathophysiological conditions induce renin release from the secretory granules of the juxtaglomerular cells of the kidney (c.f. (2)). Once released into circulation, renin exhibits high specificity for the plasma α-globulin angiotensinogen. Angiotensinogen is continuously synthesized and released from the liver into circulation. While several hormones, including Ang II itself, may regulate the synthesis of angiotensinogen, the concentration of angiotensinogen itself is not rate-limiting in the synthesis of Ang II. Renin cleaves the 10 N-terminal amino acids from angiotensinogen to produce the biologically inactive precursor, Ang I. Subsequently, the decapeptide Ang I serves as a substrate for the dipeptidyl carboxypeptidase angiotensin converting enzyme (ACE), an indiscriminate enzyme which cleaves dipeptides from substrates with dissimilar sequences. The potent vasodilator bradykinin also serves as a substrate for ACE. One of the determinants of ACE substrate selectivity is that the penultimate amino acid must be a proline, which explains why ACE does not inactivate Ang II. Once produced, Ang II is known to exert its diverse effects by acting at membrane bound receptors present on several peripheral target tissues, such as kidney, adrenal cortex, heart and vascular smooth muscle (1). In addition to its many peripheral effects, all of the components of the RAS have also been localized in the central nervous system (3). Moreover, it is now recognized that many of the physiological, endocrinological and behavioral actions of Ang II are mediated by specific receptors present in the brain (4).
KeywordsHeparin Proline Angiotensin Renin Neuroblastoma
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