AGE-DEPENDENT CHANGES IN THE BETA-ADRENOCEPTOR-G-PROTEIN(S)-ADENYLYL CYCLASE SYSTEM IN HUMAN RIGHT ATRIUM

With increasing age, cardiac beta-adrenoceptor function decreases. To study possible mechanisms underlying this process, we assessed in righ t atrial appendages from 52 patients of different ages (group A, <20 y ears, mean age 3.7 +/- 1.0 years, n = 20; group B, 20-50 years, mean a ge, 37.9 +/- 2.3 years, n = 9; group C, >50 years, mean age 66.1 +/- 1 .5 years, n = 23) without apparent heart failure who were undergoing o pen heart surgery beta-adrenoceptor number and subtype distribution (b y (-)-[I-125]-iodocyanopindolol [ICYP] binding), adenylyl cyclase acti vity, and G(s)- and G(i)-protein alpha-subunits (by quantitative Weste rn blotting). beta-Adrenoceptor number in the three groups was not sig nificantly different; in contrast, basal, 10 mu M GTP-, 100 mu M isopr enaline (ISO), 10 mM NaF-, 100 mu M forskolin-, and 10 mM Mn2+ stimula ted adenylyl cyclase activity was significantly higher in group A than in group B and was further decreased in group C. Similarly, 100 mu M terbutaline-, 100 mu M histamine-, and 100 mu M 5-HT-stimulated adenyl yl cyclase activity significantly decreased from group A to group C. M oreover, all these adenylyl cyclase parameters were significantly nega tively correlated with the age of the patients. Although G(s alpha) wa s not altered, G(i alpha) group C was significantly higher than in gro up A; moreover, there was a weak but significant positive correlation between G(i alpha) and the age of the patients. We conclude that an im pairment of the activity of the catalytic unit of adenylyl cyclase is involved in the decrease in cardiac beta-adrenoceptor function with ag e; an increase in G(i alpha) might contribute further to the reduced b eta-adrenoceptor function.