ANGIOTENSIN CONVERTING ENZYME IN THE BRAIN, TESTIS, EPIDIDYMIS, PITUITARY GLAND AND ADRENAL GLAND (CAPTOPRIL, EUKEPHALIN CONVERTASE, PEPTIDASE, CORPUS STRIATUM, GUANIDINOETHYL MERCAPTOSUCCINIC ACID)

('3)H Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of ('3)H captopril binding with enzymatic activity demonstrate the selectivity of ('3)H captopril labeling of ACE. ('3)H Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. ('3)H Captopril association with ACE is entropically driven.; The selectivity of ('3)H captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1 and 7 d after birth. There is no evidence for endogenous angiotensin II or angiotensin II receptors in such a pathway. This localization was confirmed by immuno-histochemical studies with a monoclonal anti-rat lung ACE antibody. ACE purified from the corpus stiatum has a M(,r) of 165,000 whereas lung ACE has a M(,r) of 175,000. The only difference between the native conformations of lung and striatal ACE we have found is their cleavage of amidated peptides. Substance P is an amidated neuropeptide found in a striatonigral pathway which is cleaved in a unique manner by striatal ACE.; In the male reproductive system, ('3)H captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. The initial segment of the epididymis contains very low levels of ('3)H captopril binding, while the head to of the epididymis has intense epithelial labeling. In a progression to the tail of the epididymis epithelial labeling declines and luminal grains increase. Three types of epididymal ACE can be distinguished by immunological and solubility properties. Developmental and hypophesectomy studies confirm that particulate epididymal ACE is not derived from testicular ACE.; In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment.; The general use of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor ('3)H GEMSA.