Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase.

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Research Abstract Details 

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Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Abstract Text:

Ulrich Schaefer,Sandra Vorlova,Takuji Machida,Jerry P Melchor,Sidney Strickland,Roberto Levi,

Sympathetic neurons synthesize, transport, and release tissue-type plasminogen activators (t-PAs) and urinary-type plasminogen activators (u-PAs). We reported that t-PA enhances sympathetic neurotransmission and exacerbates reperfusion arrhythmias. We have now assessed the role of u-PA and plasminogen. Neurogenic contractile responses to electrical field stimulation (EFS) were determined in vasa deferentia (VD) from mice lacking t-PA (t-PA(-/-)), plasminogen activator inhibitor-1 (PAI-1(-/-)), plasminogen (plgn(-/-)), u-PA (u-PA(-/-)), and wild-type (WT) controls. Similar levels of t-PA were present in VD and cardiac synaptosomes of WT, PAI-1(-/-), plgn(-/-), and u-PA(-/-) mice, whereas t-PA was undetectable in t-PA(-/-) tissues. EFS responses were potentiated and attenuated in VD from PAI-1(-/-) and t-PA(-/-) mice, respectively, but indistinguishable from WT responses in VD from plgn(-/-) and u-PA(-/-) mice. Moreover, t-PA inhibition with t-PA(stop) decreased EFS response in WT mice, whereas u-PA(stop) did not. VD responses to ATP, norepinephrine, and K(+) in t-PA(-/-), PAI-1(-/-), plgn(-/-), and u-PA(-/-) mice were similar to those in WT, whereas t-PA(stop) did not modify VD responses to norepinephrine in WT, t-PA(-/-), and PAI-1(-/-) mice, indicating a prejunctional site of action for t-PA-induced potentiation of sympathetic neurotransmission. Indeed, K(+)-induced norepinephrine exocytosis from cardiac synaptosomes was potentiated in PAI-1(-/-), attenuated in t-PA(-/-) and not different from WT in u-PA(-/-) and plgn(-/-) mice. Likewise, ATP exocytosis was decreased in t-PA(-/-) and attenuated by t-PA(stop) in WT mice. Thus, t-PA-induced enhancement of sympathetic neurotransmission is a prejunctional event associated with increased transmitter exocytosis and independent of u-PA and plasminogen availability. This novel t-PA action may be a potential therapeutic target in hyperadrenergic states.

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Publishing Authors By Initials

U Schaefer,S Vorlova,T Machida,JP Melchor,S Strickland,R Levi,

For similar urogenital system: genitalia: genitalia, male: vas deferens research abstracts see: urogenital system: genitalia: genitalia, male: vas deferens research

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MEDLINE DATE:

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of pharmacology and experimental thera

VOLUME: 322

Page Numbers: 265-73

Journal Abbreviation: J. Pharmacol. Exp. Ther.

ISSN: 0022-3565

DAY: 11

MONTH: 04

YEAR: 2007

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376362

Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Keywords Mesh Terms:

KEYWORDS: Vas Deferens

MESH TERMS: physiology

Chemical & Substance for Abstract: Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase. Information

Substance Name: Urinary Plasminogen Activator

Registry Number: EC 3.4.21.73

Grant and Affiliation Information for Modulation of sympathetic activity by tissue plasminogen activator is independent of plasminogen and urokinase.

AFFILIATION: Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10021, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS38472

ACRONYM: NS

MEDLINETA: J Pharmacol Exp Ther

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