BETA ADRENERGIC RECEPTOR (BAR) BINDING CHARACTERISTICS AND ADENYLATE CYCLASE (AC) ACTIVITY IN THE PULMONARY ARTERY (PA) AND THORACIC AORTA (AO)

Abstract

In vascular smooth muscle, stimulation of BAR activates AC, leading to increased cAMP production and smooth muscle relaxation. The mechanisms involved in BAR stimulation and AC activation may differ in the pulmonary vs. systemic circulation. We examined BAR binding characteristics and AC activity in the PA and AO of adult male Sprague-Dawley rats. In each experiment, membrane preparations were made from tissue pooled from 5 rats. BAR number at saturation (Bmax) and the dissociation constant (Kd) were determined in Scatchard analyses with (125I) iodocyanopindolol, 10 to 100 pM. Alprenolol, 10−5M, was used to assess nonspecific binding. Basal AC activity and that stimulated by isoproterenol (Iso, 10−5M) were measured by radioimmunoassay for cAMP. Six experiments were performed. We found that BAR Bmax was greater in PA than in AO (403±70 vs 235±18 pmoles/mg protein, M±SEM, p<0.05), and that BAR Kd was lower (i.e., affinity was higher) in PA compared to AO (38±5 vs 61±9 pH, p<0.05). Basal AC activity was similar in PA and AO (1.5±0.4 vs 1.2±0.2 pmoles cAMP/mg protein/min), as was Iso-stimulated activity (3.1±1.8 vs 2.2±0.8). We conclude that BAR density and affinity are greater in PA than in AO in the adult male rat. Findings of similar basal and beta-stimulated AC activity may indicate that the coupling of BAR to AC differs in the two vascular beds. Further characterization of BAR binding and coupling to AC in PA smooth muscle will enhance our understanding of the regulation of pulmonary vascular tone.