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Characterization of an Inhibitor of Neuronal Plasminogen Activator Released by Heart Cells

Pittman, Randall N. and Patterson, Paul H. (1987) Characterization of an Inhibitor of Neuronal Plasminogen Activator Released by Heart Cells. Journal of Neuroscience, 7 (9). pp. 2664-2673. ISSN 0270-6474. PMCID PMC6569127. doi:10.1523/jneurosci.07-09-02664.1987.

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A basic understanding of growth cone dynamics and developmental events involving growth cones requires an understanding of the function and regulation of molecules associated with and released by growth cones. Rat sympathetic neurons in culture release a urokinase-like plasminogen activator from their distal processes and/or growth cones (Pittman, 1985a). When sympathetic neurons are grown in cocultures with heart cells, however, plasminogen activator activity is not detected. The absence of plasminogen activator activity in cocultures of sympathetic neurons and heart cells appears to be due to the release of an inhibitor of plasminogen activator by heart cells. This inhibitor has a molecular weight of approximately 50 kDa in the presence of SDS and apparent molecular weights of approximately 50 and greater than 2000 kDa under native conditions. A significant fraction of the large- molecular-weight form of the inhibitor is converted to the smaller form following treatment with heparinase. Extremely stable complexes of 68 and 80 kDa are formed between the heart inhibitor and the plasminogen activator, urokinase, such that the complexes withstand boiling in SDS/mercaptoethanol. The data are consistent with the formation of an 80 kDa urokinase-inhibitor complex in the presence of heparan sulfate proteoglycan and a 68 kDa complex in the absence of heparan sulfate proteoglycan. A highly purified preparation of the heart inhibitor produces a 2- to 3-fold increase in neurite outgrowth from sympathetic neurons. These data indicate that the activity of the plasminogen activator released by sympathetic neurons can be regulated by a normal target tissue and that this regulation may result in increased neurite outgrowth from the neurons.

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Additional Information:© 1987 Society for Neuroscience. For the first six months after publication SfN’s license will be exclusive. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license ( Received August 5, 1986; revised Mar. 13, 1987; accepted Mar. 29, 1987. This work was supported by a Grant-In-Aid from the American Heart Association with funds contributed in part by the Pennsylvania Affiliate and by B.R.S.G. S07-RR-05415-24 (to R.N.P.) and by grants from the NINCDS and McKnight Foundation (to P.H.P.). We wish to thank Doreen McDowell and Paulette Midgette for excellent technical assistance.
Funding AgencyGrant Number
American Heart Association, Pennsylvania AffilliateUNSPECIFIED
National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)UNSPECIFIED
McKnight FoundationUNSPECIFIED
Issue or Number:9
PubMed Central ID:PMC6569127
Record Number:CaltechAUTHORS:20160517-103337255
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Official Citation:Characterization of an inhibitor of neuronal plasminogen activator released by heart cells RN Pittman and PH Patterson The Journal of Neuroscience, 1 September 1987, 7(9):2664-2673
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67156
Deposited By: Ruth Sustaita
Deposited On:17 May 2016 19:42
Last Modified:11 Nov 2021 00:28

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