Faculty Collaboration Database

Characterization of purine receptors in fetal lamb pulmonary circulation. Pediatr Res 2000 Jan;47(1):114-20

Date

01/07/2000

Pubmed ID

10625091

DOI

10.1203/00006450-200001000-00020

Scopus ID

2-s2.0-0033982179 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

Activation of P1 purinergic receptors by adenosine and P2 receptors by ATP plays an important role in pulmonary vasodilation that occurs at birth in fetal lambs. Purine receptors occur in several subtypes, and the effects of their stimulation vary with the specific type involved. We characterized the subtypes of P1 receptors in fetal lamb pulmonary circulation at 128-132 d gestation by investigating the effects of the following adenosine analogs: N6-cyclopentyl adenosine (A1 selective), 2-phenylaminoadenosine (A2 selective), 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (A2A selective), N6-benzyl-5'-N-ethylcarboxamidoadenosine (A3 selective), and adenosine and 5'-N-ethylcarboxamidoadenosine (nonselective). We repeated the studies after treatment of animals with A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine or A2 antagonist 1,3-dipropyl-7-methylxanthine. Identification of P2 receptors was done by investigation of the effects of P2x agonist beta,gamma-methylene-L-ATP and P2x and P2y agonist ATP. The studies were repeated after the treatment of animals with P2x antagonist suramin and the P2y antagonist cibacron blue. N6-cyclopentyl adenosine caused a significant decrease in heart rate and did not change pulmonary blood flow or pulmonary vascular resistance (PVR). The effect of N6-cyclopentyl adenosine on heart rate was abolished by 1,3-dipropyl-8-cyclopentylxanthine but not by 1,3-dipropyl-7-methylxanthine. 2-Phenylaminoadenosine, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine, 5'-N-ethylcarboxamidoadenosine, and adenosine caused significant increases in pulmonary flow and decreases in PVR, and their vasodilator effects were attenuated by the A2 antagonist 1,3-dipropyl-7-methylxanthine and not by 1,3-dipropyl-8-cyclopentylxanthine. N6-benzyl-5'-N-ethylcarboxamidoadenosine did not alter pulmonary flow or PVR. The P2x agonist beta,gamma-methylene-L-ATP caused a decrease in heart rate and had no effect on pulmonary flow and PVR. ATP caused a significant increase in pulmonary flow and decrease in PVR without affecting heart rate. The vasodilator effects of ATP were attenuated by cibacron blue and not by suramin. These data demonstrate that adenosine and ATP cause pulmonary vasodilation by activation of A2A and P2y receptors, respectively, in fetal lambs.

Author List

Konduri GG, Forman K, Mital S

Author

Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

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

Animals
Blood Pressure
Blood Vessels
Female
Heart Rate
Lung
Pregnancy
Purinergic Agonists
Receptors, Purinergic
Regional Blood Flow
Sheep