Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver.
beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[125I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase.
Katz
M S
MS
Boland
S R
SR
Schmidt
S J
SJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008099:Liver / Q000201:enzymology* / Q000254:growth & development; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D004224:Diterpenes; D006131:Growth Inhibitors; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C029247:3-iodopindolol; D006160:Guanosine Triphosphate; D010869:Pindolol; D000262:Adenylyl Cyclases; D005459:Fluorides