Effects of noradrenaline and neuropeptide Y on rat mesenteric microvessel contraction.
We have studied the contractile effects of the sympathetic transmitter noradrenaline and its cotransmitter neuropeptide Y (NPY) given alone and in combination on isolated rat mesenteric resistance vessels (200-300 microns diameter). Noradrenaline and NPY each concentration-dependently contracted rat mesenteric microvessels (EC50 approximately equal to 800 nM and 10 nM, respectively), but noradrenaline caused considerably greater maximal effects than NPY (14.3 mN vs. 3.5 mN). A low antagonistic potency of yohimbine indicated that the response to noradrenaline did not involve alpha 2-adrenoceptors, and the subtype-selective antagonists 5-methylurapidil, tamsulosin and chloroethylclonidine indicated mediation via an alpha 1A-adrenoceptor. Shallow Schild regressions for prazosin and 5-methylurapidil indicated that an alpha 1-adrenoceptor subtype with relatively low prazosin affinity might additionally be involved. Studies with the NPY analogues PYY, [Leu31, Pro34] NPY and NPY18-36 demonstrated that NPY acted via a Y1 NPY receptor. In addition to its direct vasoconstricting effects NPY also lowered the noradrenaline EC50 but did not appreciably affect maximal noradrenaline responses indicating possible potentiation. The potentiating NPY response occurred with similar agonist potency as the direct contractile NPY effects and also via a Y1 NPY receptor. The Ca2+ entry blocker nitrendipine (300 nM) reduced direct contractile responses to noradrenaline and NPY but did not affect the potentiation response to NPY.
Chen
H
H
Department of Medicine, University of Essen, Germany.
Fetscher
C
C
Schäfers
R F
RF
Wambach
G
G
Philipp
T
T
Michel
M C
MC
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007928:Lethal Dose 50; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D009478:Neuropeptide Y; D010446:Peptide Fragments; D011942:Receptors, Adrenergic, alpha; D017476:Receptors, Neuropeptide Y; D014662:Vasoconstrictor Agents; C059889:neuropeptide Y (18-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D009638:Norepinephrine