Inhibition of neuropeptide Y-induced potentiation of noradrenaline-induced vasoconstriction by PP56 (D-myo-inositol 1,2,6-tris-phosphate).
1. Although neuropeptide Y (NPY) is a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide potentiate the noradrenaline-induced contractions in rabbit gastroepiploic and femoral arteries, and guinea-pig mesenteric and uterine arteries. 2. The potentiating effect of NPY on noradrenaline-induced contraction was present in endothelium-denuded femoral arteries. 3. The potentiating effect of NPY on noradrenaline-induced contraction was antagonized by PP56 (D-myo-inositol 1,2,6-trisphosphate) in low concentrations (down to 0.1 nM). This antagonistic effect was observed in all four types of vessels studied. Contractions induced by noradrenaline, histamine, endothelin-1 and potassium were not altered by PP56 in concentrations upto 1 microM in femoral artery of rabbit. 4. We provide evidence that a non-peptide (PP56) can selectively antagonize NPY-induced effects in rabbit and guinea-pig peripheral arteries without affecting the vasoconstrictor response to noradrenaline.
Adamsson
M
M
Department of Experimental Research, Malmö General Hospital, Sweden.
Fallgren
B
B
Edvinsson
L
L
D000818:Animals; D004357:Drug Synergism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D014662:Vasoconstrictor Agents; C059368:atrinositol; D009638:Norepinephrine