Developmental changes in adenylyl cyclase and GTP binding proteins in brown fat.
During the perinatal period, norepinephrine (NE)-stimulated adenylyl cyclase activity increased in interscapular brown adipose tissue (IBAT) membranes and then declined to adult levels by 23 days postpartum. The developmental patterns of NE- and NaF-stimulated activities were identical, indicating that the developmental increase in transmitter-stimulated activity resulted from the increased interaction of alpha-subunit of guanine nucleotide-binding stimulatory protein of adenylyl cyclase (Gs alpha) with the catalytic subunit (C). This increased Gs alpha-C interaction was the result of an increase in Gs alpha specific activity, as assessed in cyc- reconstitution assays, as well as an increased C activity, as assessed by forskolin-Mn(2+)-stimulated adenylyl cyclase activity. Although adenylyl cyclase activity increased during the perinatal period, total Gs alpha levels significantly declined because of the loss of the small-molecular-mass form of Gs alpha. Thus the ratio of large to small form of Gs alpha increased threefold and might have contributed to the perinatal increase in activity. Gi alpha-like proteins, as assessed by pertussis toxin-catalyzed [32P]ADP ribosylation, declined dramatically after birth. However, this loss of Gi alpha did not contribute to developmental changes in adenylyl cyclase activity because pertussis toxin treatment failed to alter NE-stimulated activity. In contrast to G alpha subunits, there were no changes in membrane levels of G beta subunits.
Chaudhry
A
A
Laboratory of Biochemical Pharmacology, Sinai Research Institute, Detroit, Michigan 48235.
Granneman
J G
JG
D000262:Adenylyl Cyclases / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007120:Immunochemistry; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D008223:Lymphoma / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D014407:Tumor Cells, Cultured
D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine