D-myo-inositol 1,2,6-trisphosphate blocks neuropeptide Y-induced facilitation of noradrenaline-evoked vasoconstriction of the mesenteric bed.
Perfusion of the rat mesenteric bed with 0.1 or 10 nM neuropeptide Y potentiated the noradrenaline-induced increase in mesenteric pressure; the peptide did not modify basal perfusion pressure. While perfusion with 0.1 nM neuropeptide Y significantly increased the maximal noradrenaline-evoked vasoconstriction without modifying its EC50, 10 nM neuropeptide Y potentiated the maximal noradrenaline effect and significantly shifted its concentration-response curve to the left. Perfusion with 1-10 microM D-myo-inositol 1,2,6-trisphosphate (alpha-trinositol) reduced, in a concentration-dependent fashion, the neuropeptide Y-induced potentiation of the noradrenaline-evoked vasoconstriction without altering the potency or maximal response evoked by the catecholamine alone. Perfusion with 0.1 nM neuropeptide Y plus 1 microM alpha-trinositol completely abolished the neuropeptide Y-induced facilitation of the noradrenaline effect. alpha-Trinositol 1 microM in the presence of 10 nM neuropeptide Y caused a nonparallel rightward shift of the noradrenaline concentration-response curve as compared to that obtained in the presence of 10 nM neuropeptide Y alone. The alpha-trinositol blockade of the facilitatory action of neuropeptide Y was reversible.
Donoso
M V
MV
Department of Physiology, Faculty of Biological Sciences, P. Catholic University of Chile, Santiago.
Boric
M
M
Prado
M
M
Fournier
A
A
St Pierre
S
S
Edvinsson
L
L
Huidobro-Toro
J P
JP
D000818:Animals; D007295:Inositol Phosphates / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D007295:Inositol Phosphates; D009478:Neuropeptide Y; C059368:atrinositol; D009638:Norepinephrine