Inhibition of neuropeptide Y‐induced augmentation of noradrenaline‐induced vasoconstriction by D‐myo‐inositol 1,2,6‐trisphosphate in the rat mesenteric arterial bed

Publisher Website
Google Scholar
Abstract
The effect of the neuropeptide Y antagonist D‐myo‐inositol‐l,2,6‐trisphosphate (α‐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 α‐trinositol (1μM), producing a shift to the right of the dose‐response curve. A lower concentration of α‐trinositol (0.1μM)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 α‐trinositol at concentrations of up to 10μM. α‐Trinositol did not significantly antagonize neuropeptide Y‐induced augmentation of vasoconstrictor responses to sympathetic nerve stimulation, α‐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 (5μM) to block sympathetic neurotransmission, 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 α‐trinositol (1μM). These results suggest that α‐trinositol can be a useful functional antagonist of neuropeptide Y‐induced augmentation of vasoconstrictor responses to noradrenaline in the rat mesenteric arterial bed. Antagonistic effects of α‐trinositol on neuropeptide Y‐mediated pre‐junctional inhibition of sensory‐motor neurotransmission were not evident.

This publication has 26 references indexed in Scilit: