Various biologically active peptides including angiotensins, kinins, substance P and their analogs can have significant effects on gastrointestinal physiology and may precipitate in some pathological conditions of the gastrointestinal tract. These peptides are rapidly formed, converted and inactivated in vivo and exert their biologic effects at or near their sites of metabolism. Utilizing techniques of enzyme assay, subcellular fractionation and immunologic analysis, we are studying a group of specific gastrointestinal enzymes which metabolize these peptides. These enzymes include: kallikrein, renin, angiotensin I converting enzyme, aminopeptidase M and A, post-proline cleaving enzyme, neutral endopeptidase, dipeptidylaminopeptidase IV and carboxypeptidase N and P. The subcellular localization of each identified enzyme is determined in addition to its capacity to differentially metabolize various active peptides. Enzymes found on the vascular surface membrane will be studied with regard to the manner in which the enzyme/membrane association may be related to secretion of the enzyme into the circulation, modulated by conditions such as hypoxia and induced by chronic treatment with agents such as captopril (SQ 14225). Captopril, an orally administered inhibitor of angiotensin I converting enzyme, may represent the first of many orally active drugs which can inhibit kinin and angiotensin metabolizing enzymes. Knowledge of the distribution, subcellular localization and characteristics of these enzymes within the gastrointestinal tract will help us to understand their role in gastrointestinal physiology and pathology.
| Churchill, L; Bausback, H H; Gerritsen, M E et al. (1987) Metabolism of opioid peptides by cerebral microvascular aminopeptidase M. Biochim Biophys Acta 923:35-41 |
| Bausback, H H; Ward, P E (1986) Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. Adv Exp Med Biol 198 Pt A:397-404 |
| Churchill, L; Ward, P E (1986) Relaxation of isolated mesenteric arteries by des-Arg9-bradykinin stimulation of B1 receptors. Eur J Pharmacol 130:11-8 |
| Bausback, H H; Ward, P E (1986) Degradation of low-molecular-weight opioid peptides by vascular plasma membrane aminopeptidase M. Biochim Biophys Acta 882:437-44 |
| Palmieri, F E; Bausback, H H; Churchill, L et al. (1986) Kinin and enkephalin conversion by an endothelial, plasma membrane carboxypeptidase. Biochem Pharmacol 35:2749-56 |
| Palmieri, F E; Petrelli, J J; Ward, P E (1985) Vascular, plasma membrane aminopeptidase M. Metabolism of vasoactive peptides. Biochem Pharmacol 34:2309-17 |
