An Arg-Gly-Asp peptide stimulates constriction in rat afferent arteriole.
The potential role of integrins in the myogenic mechanism was studied in the rat afferent arteriole (AA) by fluorescence immunolocalization and microperfusion of isolated AA. Confocal fluorescence images were acquired from frozen sections of rat kidney after indirect immunostaining for various integrin beta- and alpha-subunits. The beta 1-, beta 3-, alpha 3-, alpha 5-, and alpha V-integrins were found on the plasma membrane in smooth muscle of AA, providing the morphological basis for participation of integrins in mechanotransduction. With 1 mM nitro-L-arginine methyl ester (L-NAME) in the luminal perfusate to inhibit endogenous nitric oxide (NO) production from AA, the hexapeptide GRGDSP (10(-7)-10(-3)M) induced immediate vasoconstriction. The constriction was dose dependent and specific or peptides with arginine-glycine-aspartic acid (RGD) motifs, commonly found on the binding sites of extracellular matrix to integrins. In controls, the hexapeptide GRGESP induced no constriction. GRGDSP, 1 mM, induced a 21.6 +/- 2.6% decrease (P < 0.05, n = 6) in lumen diameter for 30 s and an 18.3 +/- 4.1% increase (P < 0.05, n = 6) in smooth muscle intracellular calcium concentration for 18 s, as measured by the emission ratio of Fluo-3/Fura Red. Binding of exogenous RGD motifs with exposed integrins on AA smooth muscle therefore triggers calcium-dependent vasoconstriction. However, the dose response to RGD was not sensitive to the myogenic tone of the vessel, which suggests that the integrin-mediated vasoconstriction is different from myogenic constriction.
Yip
K P
KP
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Marsh
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D048429:Cell Size; D039422:Integrin alpha3; D039482:Integrin alpha5; D039564:Integrin alphaV; D019012:Integrin beta1 / Q000032:analysis / Q000502:physiology; D039661:Integrin beta3; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009399:Nephrons / Q000098:blood supply; D009842:Oligopeptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*
D015703:Antigens, CD; D039422:Integrin alpha3; D039482:Integrin alpha5; D039564:Integrin alphaV; D019012:Integrin beta1; D039661:Integrin beta3; D016023:Integrins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; C058347:glycyl-arginyl-glycyl-glutamyl-seryl-proline; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester