Relative contribution of intracellular and extracellular Ca2+ to α2-adrenoceptor-mediated contractions of ovine pulmonary artery

K. Sathishkumar, Gracious R. Ross, Vellanki Ravi Prakash, Santosh K. Mishra

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We have examined the mechanism of contractions elicited by guanfacine, a selective agonist for α2A/D-adrenoceptors and its modulations by cyclic nucleotides in isolated ovine resistance intra-pulmonary artery. Guanfacine (10 nM-30 μM) produced concentration-dependent contraction of the pulmonary artery rings mounted for isometric recording. Yohimbine (0.1 μM), a nonspecific α2-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 Ca2+-free solution (EGTA 1 mM) 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 μM) slightly inhibited (20%) the maximal contraction elicited with guanfacine (10 μM). On the other hand, brief exposure to cyclopiazonic acid (10 μM), an inhibitor of IP3-sensitive sarcoplasmic reticulum Ca2+-ATPase, resulted in marked inhibition of concentration-dependent contractions elicited with guanfacine (10 nM-30 μM), 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 α2-adrenoceptor-mediated contractions in ovine resistance pulmonary artery is primarily dependent on intracellular Ca2+ with a small contribution from Ca2+-influx through voltage-dependent L-type calcium channels.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalPharmacological Research
Volume54
Issue number3
DOIs
StatePublished - Sep 1 2006

Keywords

  • Contraction
  • Guanfacine
  • Intracellular calcium
  • Pulmonary artery
  • α-adrenoceptors

ASJC Scopus subject areas

  • Pharmacology

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