Systemic ovalbumin sensitization downregulates norepinephrine uptake by rabbit aortic smooth muscle cells.
Norepinephrine (NE) concentration at alpha-adrenergic receptors is partially regulated by steroid-sensitive, extraneuronal catecholamine uptake (uptake-2). Because alpha(1)-adrenergic agonist- and glucocorticosteroid (GS)-induced bronchial vasoconstriction is enhanced in individuals with asthma, atopy could be associated with decreased uptake-2 by vascular smooth muscle cells (SMCs). We therefore evaluated whether NE uptake and its specific transporter messenger RNA (mRNA) were reduced in aortic SMCs of rabbits systemically sensitized with ovalbumin (OVA). NE uptake was measured using a semiquantitative fluorescence microscopic method. Corticosterone and O-methyl-isoprenaline, but not desipramine, co-incubation (1 micro M each) for 20 min decreased NE uptake into SMCs, an inhibitor profile indicative of extraneuronal monoamine transporter (EMT). In OVA-sensitized rabbits, NE uptake was 25.9 +/- 4.5% (mean +/- SEM) lower than in control animals (P < 0.05). Sensitized serum had no effect on NE uptake into naive SMCs. EMT mRNA expression was measured in aortic smooth muscle, using multiplex reverse transcriptase-polymerase chain reaction. In OVA-sensitized rabbits, expression was 61.1 +/- 16.4% lower than in control animals (P < 0.05). These data demonstrate that NE uptake by aortic SMCs is impaired in atopic rabbits, and associated with a decreased transporter mRNA expression. The same mechanism may operate in bronchial arteries in individuals with asthma.
Horvath
Gabor
G
Division of Pulmonary and Critical Care Medicine, and Department of Cell Biology and Anatomy, University of Miami School of Medicine, Miami, Florida 33101, USA.
Torbati
Aliza
A
Conner
Gregory E
GE
Salathe
Matthias
M
Wanner
Adam
A
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D001249:Asthma / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000493:pharmacokinetics*; D027701:Organic Cation Transport Proteins; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D000099254:Organic Cation Transporter 3
D000316:Adrenergic alpha-Agonists; D002352:Carrier Proteins; D009638:Norepinephrine; D027701:Organic Cation Transport Proteins; D010047:Ovalbumin; D012333:RNA, Messenger; D000099254:Organic Cation Transporter 3