213 β-ADRENERGIC RECEPTORS AND ADENYLATE CYCLASE IN DEVELOPING RAT MYOCARDIUM

Abstract

β-Adrenergic receptors (BAR) were identified in rat myocardium during development with [3H] dihydroalprenolol, [3H] DHA and [125I]iodohydroxybenzylpindolol, [125I]HYP. Heart weight, protein and the number of BAR per cell increased with age, however Bmax per mg protein decreased progressively with age and was lower in adult 36.8±4.1 as compared to the neonatal rat, 58.3±7.2 fmoles·mg−1 protein, m±SE, p<0.01. While Na+, K+-ATPase, 5′-nucleotidase and adenylate cyclase (AC) increased equally to or in excess of ventricular protein; the developmental increase in [3H]DHA binding per heart did not keep up with the increases in protein during growth. BAR subtypes did not change with age: 75% β1 and 25% β2. Guanine nucleotides (GN) decreased agonist affinity for the inhibition of [125I]HYP binding equally in adult and fetal samples and enhanced the activation of AC by catecholamines. The lower specific activity (per mg protein) of BAR in adult myocardium may be related to the decreasing proportion of sarcolemmal protein as compared to total cell protein which occurs during hypertrophic cardiac growth, supporting the hypothesis that sarcolemmal area is a major determinant of BAR number. The function of BAR is mediated by GN's early in development, and observed age dependent differences in the activation of AC by GTP and Gpp(NH)p may relate to developmental differences in the properties of GN dependent factors which mediate receptor occupancy and c-AMP production “coupling”.