In an effort to define the mechanisms regulating pulmonary vasodilatation and explain the greater in vitro response to isoproterenol 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 X̄ ± 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 μM, P < .05), as was affinity for l-epinephrine (0.89 ± 0.20 vs. 3.87 ± 0.62 μM, P < .05). Affinity was similar for l-norepinephrine (18.93 ± 3.63 vs. 13.49 ± 3.12 μM). 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 < .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 < .05). Enzyme activity stimulated by GTP was similar in the two arteries (11.9 ± 2.6 vs. 10.0 ± 2.9, PA vs. AO). Enzyme activity stimulated by isoproterenol plus GTP was greater in PA than in AO (25.2 ± 4.2 vs. 12.4 ± 2.5, P < .05), as was activity stimulated by forskolin (182.9 ± 10.0 vs. 114.9 ± 9.7, P < .05). These findings suggest that the greater vasodilatory response to isoproterenol found in vitro in PA compared to AO may be due to greater activated adenylate cyclase activity secondary to greater receptor affinity for the agonist and/or enhanced function of the catalytic moiety of the enzyme.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1990|
ASJC Scopus subject areas
- Molecular Medicine