Inhibition of neuropeptide Y-induced augmentation of noradrenaline-induced vasoconstriction by D-myo-inositol 1,2,6-trisphosphate in the rat mesenteric arterial bed.
The effect of the neuropeptide Y antagonist D-myo-inositol-1,2, 6-trisphosphate (alpha-trinositol) was tested against modulatory actions mediated by neuropeptide Y in the isolated rat mesenteric arterial bed. Neuropeptide Y (1 and 10 nM) had no direct postjunctional effects, but augmented vasoconstrictor responses to noradrenaline and to sympathetic nerve stimulation to an extent which was greater with the higher concentration of neuropeptide Y. The augmenting effect of neuropeptide Y at 1 nM on vasoconstriction induced by lower doses of noradrenaline was antagonized by alpha-trinositol (1 microM), producing a shift to the right of the dose-response curve. A lower concentration of alpha-trinositol (0.1 microM) had no inhibitory effect on responses to noradrenaline. Augmentation by the higher concentration of neuropeptide Y (10 nM) of noradrenaline-induced vasoconstriction was not affected by alpha-trinositol at concentrations of up to 10 microM. alpha-Trinositol did not significantly antagonize neuropeptide Y-induced augmentation of vasoconstrictor responses to sympathetic nerve stimulation. alpha-Trinositol alone did not affect vasoconstrictor responses to noradrenaline, potassium, or to sympathetic nerve stimulation. In the raised-tone preparation (tone raised with methoxamine) in the presence of guanethidine (5 microM) to block sympathetic neuro-transmission, perivascular nerve stimulation caused vasodilatation due to activation of sensory-motor nerves. Neuropeptide Y inhibited sensory-motor nerve induced vasodilatation in a concentration-dependent manner but this was not affected by alpha-trinositol (1 microM). These results suggest that alpha-trinositol can be a useful functional antagonist of neuropeptide Y-induced augmentation of vasoconstrictor responses to noradrenaline in the rat mesenteric arterial bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Ralevic
V
V
Department of Anatomy, University College London, UK.
Edvinsson
L
L
Burnstock
G
G
D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009046:Motor Neurons / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation; D009475:Neurons, Afferent / Q000502:physiology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D007295:Inositol Phosphates; D009478:Neuropeptide Y; C059368:atrinositol; D009638:Norepinephrine