Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD-containing peptide.
It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0% reduction). In association with the decrease in [Ca2+]i, arteriolar lumen diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1.8% dilation). At intermediate concentrations, cycloRGD induced rhythmic spiking of Ca2+ superimposed on the concentration-dependent lowering of basal [Ca2+]i. These data directly link integrin activation with alterations in Ca2+ regulation, the net effect of which is a reduction in [Ca2+]i. These data further suggest that integrins, through their role in mediating cellular attachment to the extracellular matrix and in cellular signaling involving Ca2+, could provide a logical link to mechanotransduction and myogenic phenomena.
D'Angelo
G
G
Department of Medical Physiology, Texas A&M University Health Science Center, College Station 77843-1114, USA.
Mogford
J E
JE
Davis
G E
GE
Davis
M J
MJ
Meininger
G A
GA
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014664:Vasodilation
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium