Integrin control of arteriolar function /
The arginine-glycine-aspartic acid (RGD) tripeptide sequence
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| Format: | Thesis Book |
| Language: | English |
| Published: |
[Place of publication not identified] :
[publisher not identified] ;
1997.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=739891281&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The arginine-glycine-aspartic acid (RGD) tripeptide sequence is a common binding sequence for integrins, a family of adhesion receptors known to activate several intracellular signaling pathways via ligand binding. The ability of soluble RGD peptides to alter vasomotor tone was tested using an isolated rat skeletal muscle 1A arteriole preparation. Isolated arterioles with spontaneous tone showed concentration-dependent (0.2 [tmol/L-70 mmol/L) vasodilation to topical application of the synthetic peptides GRGDNP, GRGDSP and cyclic RGD. The control peptide GRGESP had no vasomotor effect at any concentration. Removal of the endothelium did not alter the response to GRGDSP implicating vascular smooth muscle cells (VSMC's) as mediators of this response. The potency ranking of the peptides (cyclic RGD>GRGDSP>GRGDNP) parallels the reported ability of the peptides to block alpha v beta 3 integrin functions. The involvement Of (alpha v beta 3 in the RGD-induced vasodilations was demonstrated by the finding that pretreatment of arterioles with 1 00 [ig of Fl 1, a D3 integrin function blocking monoclonal antibody, significantly inhibited the cyclic RGD-induced vasodilation. Fl 1 also inhibited the vasodilation caused by proteolytic fragments of denatured collagen type 1. Collagen type I contains 7 RGD sequences per molecule; therefore, coliagen fragments may modulate tissue blood flow after proteolysis of the ECM during tissue injury through the interaction of the RGD sequence with VSMC alpha v beta 3 integrin. Blockade Of alpha v beta 3 integrin function also revealed transient vasoconstrictions in response to higher concentrations (70 gmol/L-700 mmol/L) of GRGDNP and GRGDSP. Sustained vasoconstriction was induced alone by GRGDNP, but not GRGDSP, at 2.1 mM. The sustained response was inhibited by antibody blockade Of (X501 function but was unaffected by a control anti-alpha 1 integrin antibody. The response was similarly inhibited by removal of the endothelial cells (EC) or blockade of endothelin-A receptors with BQ610 (1 limol/L). Thus, interaction of the RGDN sequence with EC (X501 appears to cause sustained endothelin-dependent arteriolar constriction. Collectively, these results support the concept that RGD-containing peptides can induce arteriolar dilation or constriction through interaction with VSMC alpha v beta 3 or EC U-501, respectively. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". |
| Physical Description: | xi, 120 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 97-118. |