Abstract
The local environment of neurosecretory cells contains the major components of the plasminogen activation system, including the plasminogen activators, tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), as well as binding sites for t-PA, the receptor for u-PA (uPAR), and also the plasminogen activator inhibitor, PAI-1. Furthermore, these cells express specific binding sites for plasminogen, which is available in the circulation and in interstitial fluid. Colocalization of plasminogen and its activators on cell surfaces provides a mechanism for promoting local plasminogen activation. Plasmin is retained on the cell surface where it is protected from its inhibitor, α2-antiplasmin. In neurosecretory cells, localized plasmin activity provides a mechanism for extracellular processing of secreted hormones. Neurotransmitter release from catecholaminergic cells is negatively regulated by cleavage products formed by plasmin-mediated proteolysis. Recently, we have identified a major plasminogen receptor, Plg-RKT. We have found that Plg-RKT is highly expressed in chromaffin cells of the adrenal medulla as well as in other catecholaminergic cells and tissues. Plg-RKT-dependent plasminogen activation plays a key role in regulating catecholaminergic neurosecretory cell function.
Highlights
Chromaffin cells of the adrenal medulla and other neurosecretory cells contain specific binding sites for plasminogen [1, 2], which is available at high concentration in the circulation and in interstitial fluid
These results suggest that the chromaffin cell plasminogen receptors that are sensitive to carboxypeptidase B (CpB) are primarily responsible
The plasminogen activation system plays a major role in catecholaminergic cell function by processing secreted hormones that feed back to regulate the neurosecretory characteristics of these cells
Summary
Chromaffin cells of the adrenal medulla and other neurosecretory cells contain specific binding sites for plasminogen [1, 2], which is available at high concentration in the circulation and in interstitial fluid These cells secrete major components of the plasminogen activation system, including the plasminogen activators tissue plasminogen activator (t-PA) [3,4,5,6,7] and urokinasetype plasminogen activator (u-PA) [4, 8], and the plasminogen activator inhibitors, PAI-1 [9] and neuroserpin [10]. In this paper we summarize the interplay between components of the local neurosecretory cell plasminogen activation system, the functional consequences of the interaction of plasmin with catecholaminergic cells, and our recent studies demonstrating the expression and function of Plg-RKT in catecholaminergic cells
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