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Characterization of the postjunctional alpha 2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins.

Abstract：

BACKGROUND AND PURPOSE:In terms of postjunctional alpha(2)-adrenoceptors in the pulmonary circulation, no evidence is available with regard to the receptor subtypes mediating vasoconstriction. Therefore, we characterized the alpha(2)-adrenoceptor subtypes mediating contraction in isolated porcine pulmonary veins. EXPERIMENTAL APPROACH:alpha-adrenoceptor-mediated vasoconstriction was studied using a tissue bath protocol. mRNA profile and relative quantification of alpha(2)-adrenoceptor subtypes were determined in porcine pulmonary veins using reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR. KEY RESULTS:In porcine pulmonary veins, noradrenaline, phenylephrine (alpha(1)-adrenoceptor agonist), UK14304 and clonidine (alpha(2)-adrenoceptor agonists) caused concentration-dependent contractions. The rank order of agonist potency was: NA approximately UK14304 approximately clonidine > phenylephrine. UK14304 responses were antagonised by MK912 (noncompetitive antagonist parameter pD'(2): 10.1), rauwolscine (pK(B): 9.5), yohimbine (pK(B): 9.1), WB4101 (pK(B): 8.7), ARC239 (pK(B): 7.5), prazosin (pK(B): 7.1) and BRL44408 (pK(B): 7.0). Antagonist potencies fitted best with radioligand binding data (pK(i)) at the human recombinant alpha(2C)-adrenoceptor (r(2)=0.96, P=0.0001). Correlation with alpha(2B)-adrenoceptors was lower (r(2)=0.74, P>0.01) and no correlation was obtained with alpha(2A)-adrenoceptors. Moreover, RT-PCR studies in porcine pulmonary veins showed mRNA signals for alpha(2A)- and alpha(2C)-adrenoceptors, but not for alpha(2B)-adrenoceptors, whilst real-time PCR studies indicated a prominent expression of alpha(2C)-adrenoceptor mRNA. CONCLUSIONS AND IMPLICATIONS:Postjunctional alpha(2C)-adrenoceptors mediated contraction in porcine pulmonary veins. alpha(1)-Adrenoceptors also seem to be present in this tissue. Since alpha(2)-adrenoceptor responsiveness is increased when pulmonary vascular tone is elevated, alpha(2C)-adrenoceptor antagonists may be beneficial in diseases such as pulmonary hypertension or congestive heart failure.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Görnemann T,von Wenckstern H,Kleuser B,Villalón CM,Centurión D,Jähnichen S,Pertz HH

doi

10.1038/sj.bjp.0707221

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

186-94

issue

eissn

0007-1188

issn

1476-5381

pii

0707221

journal_volume

151

pub_type

杂志文章

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Characterization of the postjunctional alpha 2C-adrenoceptor mediating vasoconstriction to UK14304 in porcine pulmonary veins.