Inhibition of vasoconstriction and Ca2+ currents mediated by neuropeptide Y Y2 receptors.
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 10 nM. 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.
Lewis
C J
CJ
Department of Human Physiology, Flinders University, Adelaide, Australia.
Evans
R J
RJ
Neild
T O
TO
D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000098:blood supply; D007421:Intestine, Small / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; C078948:peptide YY (13-36); D019894:Peptide YY; C062259:neuropeptide Y, Leu(31)-Pro(34)-; C087872:neuropeptide Y (24-36) amide, N-acetyl-(Leu(28,31))-; D002118:Calcium