Faculty Collaboration Database

Relative contribution of intracellular and extracellular Ca2+ to alpha2-adrenoceptor-mediated contractions of ovine pulmonary artery. Pharmacol Res 2006 Sep;54(3):219-25

Date

06/22/2006

Pubmed ID

16787748

DOI

10.1016/j.phrs.2006.05.002

Scopus ID

2-s2.0-33746345893 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

We have examined the mechanism of contractions elicited by guanfacine, a selective agonist for alpha(2A/D)-adrenoceptors and its modulations by cyclic nucleotides in isolated ovine resistance intra-pulmonary artery. Guanfacine (10 nM-30 microM) produced concentration-dependent contraction of the pulmonary artery rings mounted for isometric recording. Yohimbine (0.1 microM), a nonspecific alpha(2)-adrenoceptor antagonist caused a parallel shift to the right (1.2 log unit) in the concentration-response curve of guanfacine without depressing the maxima. Preincubation of the tissues with Ca(2+)-free solution (EGTA 1mM) for 30 min caused a rightward shift (0.8 log unit) of the concentration-response curve of guanfacine with the inhibition of the maxima by 30+/-4.6%. L-type calcium channel blocker, nifedipine (1 microM) slightly inhibited (20%) the maximal contraction elicited with guanfacine (10 microM). On the other hand, brief exposure to cyclopiazonic acid (10 microM), an inhibitor of IP3-sensitive sarcoplasmic reticulum Ca(2+)-ATPase, resulted in marked inhibition of concentration-dependent contractions elicited with guanfacine (10 nM-30 microM), with the maxima being inhibited by 51+/-3.11%. In addition, agents that increase intracellular cAMP and cGMP suppressed guanfacine-induced contractions. The results of the present study suggest that alpha(2)-adrenoceptor-mediated contractions in ovine resistance pulmonary artery is primarily dependent on intracellular Ca(2+) with a small contribution from Ca(2+)-influx through voltage-dependent L-type calcium channels.

Author List

Sathishkumar K, Ross GR, Prakash VR, Mishra SK

Author

Gracious R. Ross Research Scientist II in the Cardiovascular Center department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenergic alpha-Agonists
Animals
Calcium
Calcium Channel Blockers
Cyclic AMP
Cyclic GMP
Glyburide
Guanfacine
Indoles
Muscle Contraction
Muscle, Smooth, Vascular
Nifedipine
Nucleotides, Cyclic
Pulmonary Artery
Receptors, Adrenergic, alpha-2
Sheep
Vasoconstriction
Vasodilator Agents