Harpers

452 / CHAPTER 42AngiotensinogenAsp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu (~400 more amino acids)RENINAngiotensin IAsp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-LeuCONVERTING ENZYMEANGIOTENSIN IIAsp-Arg-Val-Tyr-Ile-His-Pro-PheAMINOPEPTIDASEAngiotensin IIIArg-Val-Tyr-Ile-His-Pro-PheANGIOTENSINASESDegradation productsFigure 42–14. Formation and metabolism of angiotensins. Small arrows indicatecleavage sites.referred to as angiotensin-converting enzyme (ACE)inhibitors. Angiotensin II increases blood pressure bycausing vasoconstriction of the arteriole and is a verypotent vasoactive substance. It inhibits renin releasefrom the juxtaglomerular cells and is a potent stimulatorof aldosterone production. This results in Na + retention,volume expansion, and increased blood pressure.In some species, angiotensin II is converted to theheptapeptide angiotensin III (Figure 42–14), an equallypotent stimulator of aldosterone production. In humans,the plasma level of angiotensin II is four timesgreater than that of angiotensin III, so most effects areexerted by the octapeptide. Angiotensins II and III arerapidly inactivated by angiotensinases.Angiotensin II binds to specific adrenal cortexglomerulosa cell receptors. The hormone-receptor interactiondoes not activate adenylyl cyclase, and cAMPdoes not appear to mediate the action of this hormone.The actions of angiotensin II, which are to stimulatethe conversion of cholesterol to pregnenolone and ofcorticosterone to 18-hydroxycorticosterone and aldosterone,may involve changes in the concentration of intracellularcalcium and of phospholipid metabolites bymechanisms similar to those described in Chapter 43.Complex Processing Generatesthe Pro-opiomelanocortin (POMC)Peptide FamilyThe POMC family consists of peptides that act as hormones(ACTH, LPH, MSH) and others that may serveas neurotransmitters or neuromodulators (endorphins)(see Figure 42–15). POMC is synthesized as a precursormolecule of 285 amino acids and is processed differentlyin various regions of the pituitary.The POMC gene is expressed in the anterior and intermediatelobes of the pituitary. The most conservedsequences between species are within the amino terminalfragment, the ACTH region, and the β-endorphinregion. POMC or related products are found in severalother vertebrate tissues, including the brain, placenta,gastrointestinal tract, reproductive tract, lung, and lymphocytes.The POMC protein is processed differently in the anteriorlobe than in the intermediate lobe. The intermediatelobe of the pituitary is rudimentary in adult humans,but it is active in human fetuses and in pregnant womenduring late gestation and is also active in many animalspecies. Processing of the POMC protein in the peripheraltissues (gut, placenta, male reproductive tract) resem-