Relative contribution of intracellular and extracellular Ca2+ to alpha2-adrenoceptor-mediated contractions of ovine pulmonary artery.
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.
Sathishkumar
K
K
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar-243 122 UP, India.
Ross
Gracious R
GR
Prakash
Vellanki Ravi
VR
Mishra
Santosh K
SK
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D016316:Guanfacine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012756:Sheep; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D007211:Indoles; D009712:Nucleotides, Cyclic; D018341:Receptors, Adrenergic, alpha-2; D014665:Vasodilator Agents; D016316:Guanfacine; D000242:Cyclic AMP; D006152:Cyclic GMP; D009543:Nifedipine; D005905:Glyburide; D002118:Calcium; C000543:cyclopiazonic acid