Characterization of purine receptors in fetal lamb pulmonary circulation

Activation of P-1 purinergic receptors by adenosine and P-2 receptors by AT P plays an important role in pulmonary vasodilation that occurs at birth in fetal lambs. Purine receptors occur in several subtypes, and the effects o f their stimulation vary with the specific type involved. We characterized the subtypes of P-1 receptors in fetal lamb pulmonary circulation at 128-13 2 d gestation by investigating the effects of the following adenosine analo gs: N-6-cyclopentyl adenosine (A(1) selective), 2-phenylaminoadenosine (A(2 ) selective), 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadeno sine (A(2A) selective), N-6-benzyl-5'-N-ethylcarboxamidoadenosine (A(3) sel ective), and adenosine and 5'-N-ethylcarboxamidoadenosine (nonselective). W e repeated the studies after treatment of animals with A(1) antagonist 1,3- dipropyl-8-cyclopentylxanthine. or A(2) antagonist 1,3-dipropyl-7-methylxan thine. Identification of P-2 receptors was done by investigation of the eff ects of P-2x agonist beta,gamma-methylene-L-ATP and P-2x and P-2y agonist A TP. The studies were repeated after the treatment of animals with P-2x anta gonist suramin and the P-2y antagonist cibacron blue. N-6-cyclopentyl adeno sine caused a significant decrease in heart rate and did not change pulmona ry blood flow or pulmonary vascular resistance (PVR). The effect of N-6-cyc lopentyl adenosine on heart rate was abolished by 1,3-dipropyl-8-cyclopenty lxanthine but not by 1,3-dipropyl-7-methylxanthine. 2-Phenylaminoadenosine, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine, 5'-N-et hylcarboxamidoadenosine, and adenosine caused significant increases in pulm onary how and decreases in PVR, and their vasodilator effects were attenuat ed by the A(2) antagonist 1,3-dipropyl-7-methylxanthine and not by 1,3-dipr opyl-8-cyclopentylxantbine. N-6-benzyl-5'-N-ethylcarboxamidoadenosine did n ot alter pulmonary flow or PVR. The P-2x agonist beta,gamma-methylene-L-ATP caused a decrease in heart rate and bad no effect on pulmonary how and PVR . ATP caused a significant increase in pulmonary flow and decrease in PVR w ithout 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 A(2A) and P-2y recep tors, respectively, in fetal lambs.