title: N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and beta-NAD in blood vessels.
abstract: Using HPLC techniques we evaluated the electrical field stimulation-evoked overflow of noradrenaline (NA), adenosine 5'-triphosphate (ATP), and beta-nicotinamide adenine dinucleotide (beta-NAD) in the presence of low nanomolar concentrations of omega-conotoxin GVIA or omega-agatoxin IVA in the canine mesenteric arteries and veins. omega-conotoxin GVIA abolished the evoked overflow of NA and beta-NAD in artery and vein, whereas the evoked overflow of ATP remained unchanged in the presence of omega-conotoxin GVIA. omega-agatoxin IVA significantly reduced the evoked overflow of ATP and beta-NAD. The overflow of NA remained largely unaffected by omega-agatoxin IVA, except at 16Hz in the vein where the overflow of NA was reduced by about 50%. Artery and vein exhibited similar expression levels of the alpha(1B) (CaV2.2, N-type) subunit, whereas the vein showed greater levels of the alpha(1A) (CaV2.1, P/Q-type) subunit than artery. Therefore, there are at least two release sites for NA, beta-NAD and ATP in the canine mesenteric artery and vein: an N-type-associated site releasing primarily NA, beta-NAD and some ATP, and a P/Q-type-associated site releasing ATP, beta-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, beta-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. beta-NAD and ATP may mediate disparate functions in the canine mesenteric resistive and capacitative circulations.
authors.affiliation: Department of Physiology and Cell Biology, Anderson Medical Sciences Building, MS 352, University of Nevada School of Medicine, 1664 N. Virginia Street, Reno, NV 89557-0352, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Smyth
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Yamboliev
authors.forename: Violeta N
authors.initials: VN
authors.lastname: Mutafova-Yambolieva
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D014680:Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D009243:NAD; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D000241:Adenosine; D009638:Norepinephrine