N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and β-NAD in blood vessels

Abstract

Using HPLC techniques we evaluated the electrical field stimulation-evoked overflow of noradrenaline (NA), adenosine 5′-triphosphate (ATP), and β-nicotinamide adenine dinucleotide (β-NAD) in the presence of low nanomolar concentrations of ω-conotoxin GVIA or ω-agatoxin IVA in the canine mesenteric arteries and veins. ω-conotoxin GVIA abolished the evoked overflow of NA and β-NAD in artery and vein, whereas the evoked overflow of ATP remained unchanged in the presence of ω-conotoxin GVIA. ω-agatoxin IVA significantly reduced the evoked overflow of ATP and β-NAD. The overflow of NA remained largely unaffected by ω-agatoxin IVA, except at 16 Hz in the vein where the overflow of NA was reduced by about 50%. Artery and vein exhibited similar expression levels of the α 1B (CaV2.2, N-type) subunit, whereas the vein showed greater levels of the α 1A (CaV2.1, P/Q-type) subunit than artery. Therefore, there are at least two release sites for NA, β-NAD and ATP in the canine mesenteric artery and vein: an N-type-associated site releasing primarily NA, β-NAD and some ATP, and a P/Q-type-associated site releasing ATP, β-NAD and some NA. The N-type-mediated mechanisms are equally expressed in artery and vein, whereas the P/Q-type-mediated mechanisms are more pronounced in the vein and may ensure additional neurotransmitter release at higher levels of neural activity. In artery, β-NAD caused a dual effect consisting of vasodilatation or vasoconstriction depending on concentrations, whereas vein responded with vasodilatation only. In contrast, ATP caused vasoconstriction in both vessels. β-NAD and ATP may mediate disparate functions in the canine mesenteric resistive and capacitative circulations.