Comparison of beta adrenergic receptor binding characteristics and coupling to adenylate cyclase in rat pulmonary artery versus aorta.
In an effort to define the mechanisms regulating pulmonary vasodilatation and explain the greater in vitro response to iso-proterenol in the pulmonary artery (PA) vs. aorta (AO), we compared beta adrenergic receptor binding characteristics and coupling to adenylate cyclase in PA and AO obtained from adult male rats. Beta adrenergic receptor binding characteristics and affinity for agonists were determined with [125I]-iodocyanopindolol. Agonist displacement studies were characteristic of a beta-2 adrenergic receptor subtype. Receptor density (44.7 +/- 7.3 vs. 39.6 +/- 0.8 fmol/mg of protein means +/- S.E.M., PA vs. AO) and the dissociation constant for the radioligand (10.3 +/- 2.6 vs. 13.4 +/- 3.5 pM) were similar in the two arteries. However, affinity for l-isoproterenol was greater (the inhibition constant was lower) in PA compared to AO (0.08 +/- 0.03 vs. 1.20 +/- 0.18 microM, P less than .05), as was affinity for l-epinephrine (0.89 +/- 0.20 vs. 3.87 +/- 0.62 microM, P less than .05). Affinity was similar for l-norepinephrine (18.93 +/- 3.63 vs. 13.49 +/- 3.12 microM). Base-line cyclic AMP (cAMP) content, basal adenylate cyclase activity and adenylate cyclase activity stimulated by GTP, isoproterenol plus GTP and forskolin were measured by radioimmunoassay for cAMP. Base-line cAMP content was greater in PA than in AO (513.5 +/- 46.9 vs. 125.5 +/- 19.1 pmol of cAMP per mg of protein, P less than .001), as was basal adenylate cyclase activity (10.8 +/- 1.2 vs. 5.7 +/- 1.3 pmol of cAMP per mg of protein per min, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Shaul
P W
PW
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
Muntz
K H
KH
Buja
L M
LM
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001665:Binding Sites; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D006160:Guanosine Triphosphate; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol