Inhibition of Vasoconstriction and Ca²⁺ Currents Mediated by Neuropeptide Y Y2 Receptors

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The effects of neuropeptide Y (NPY) and agonists selective for NPY Y1 and Y2 receptors were studied on contraction and Ca²⁺ currents in arterial smooth muscle. In isolated arterioles from the guinea-pig small intestine, small brief constrictions were evoked by depolarising the arteriolar smooth muscle using high K⁺ solution applied from a micropipette. The constrictions were reduced in amplitude by the Y2-selective agonists PYY (13-36) and N-acetyl [Leu²⁸, Leu³¹] NPY-(24-36) in concentrations from 20-100 nM. NPY or the Y1-selective agonist [Leu31 Pro34] NPY in concentrations from 50 pM to 100 nM increased the amplitude of the constrictions, with a maximum effect at 10nM. Smooth muscle cells were isolated from rat small mesenteric arteries, and voltage-activated Ca²⁺ currents measured by whole cell patch clamping. The peak amplitude of the Ca²⁺ currents was decreased by N-acetyl [Leu²⁸, Leu³¹] NPY-(24-36), and by NPY (100 nM). [Leu³¹, Pro³⁴] NPY either had no effect or slightly increased the Ca²⁺ currents. We conclude that Y2 receptors on vascular smooth muscle can reduce Ca²⁺ currents induced by depolarisation, and thus oppose constriction caused by smooth muscle depolarisation.