The nonapeptide CDPGYIGSR is localized in domain III of the b1 chain in human and mouse laminins. Previous studies revealed powerful anti-angiogenic and tumour inhibiting effects of this peptide. But so far nothing is known about the possible impact of the peptide on vascular tone. We therefore determined the effect of this molecule using isometric force measurements in mouse tail artery and aorta. Our experiments showed that CDPGYIGSR induced a strong dose-dependent vasoconstriction in small and big arteries of mouse. Thereby, the amide form CDPGYIGSR- NH2 proved more active than CDPGYIGSR-OH. Vasoconstriction by the nonapeptide was endothelium- independent but could be strongly attenuated by the L-type Ca2+ channel blocker nifedipine. The SERCA inhibitor thapsigargin in combination with nifedipine abrogated vasoconstriction almost completely. The important role of increased [Ca2+ ]i was corroborated by single-cell experiments using the Ca2+ indicator fura 2-AM. CDPGYIGSR induced [Ca2+ ]i transients that could be inhibited by nifedipine and thapsigargin.

Taken together, CDPGYIGSR elevates vascular tone by activating voltage-dependent Ca2+ channels and depleting Ca2+ stores in vascular smooth muscle cells. Thus, the extracellular matrix protein laminin appears to be also involved in the regulation of vascular tone.