Interaction of cysteine proteases with calciotropic hormone receptors.
The effect of two cysteine proteases: papain and a cathepsin L-like enzyme purified from the oesophagus of Nephrops norvegicus (NCP) was studied on the specific binding of calcitonin (CT) and calcitonin gene related peptide (CGRP) to rat kidney and liver membranes, respectively. In addition, the response of adenylyl cyclase to increasing concentrations of these two enzymes was investigated. Each protease inhibited the initial CGRP and CT binding to rat liver and kidney membranes, respectively, in a manner not significantly different from that obtained in the presence of the unlabeled standard. The adenylyl cyclase activity in rat liver membranes was increased by the addition of each enzyme. The response was higher with papain that induced a fivefold increase of enzyme activity at a 4-microg/ml enzyme concentration. In rat kidney membranes, the magnitude of the response was identical with both enzymes. In contrast with NCP, papain induced a biphasic response. Leupeptin and E(64), two specific inhibitors of cysteine proteases, reversed the observed effects. Trypsin induced an inhibition of the liver membrane adenylyl cyclase activity and an activation in rat kidney membranes at low protease concentration. Thus, cysteine proteases are able to act, in vitro, at the receptor level in target organs specific for calciotropic hormones.
Station de Biologie Marine, Muséum National d'Histoire Naturelle, BP 225. 29182 Concarneau Cedex, France. peron@mnhn.fr
M
M
Fouchereau-Peron
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D010206:Papain / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats
D002116:Calcitonin; D003546:Cysteine Endopeptidases; D010206:Papain; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide