Differential forskolin activation of rat heart and lung adenylate cyclase. Dependence on membrane-protein interactions.
We have investigated whether the greater ability of forskolin to activate adenylate cyclase (EC 4.6.1.1) from rat heart compared with rat lung is due to interactions between G-proteins and catalytic units, isoforms of catalytic units or membrane-protein interactions. Interactions between Gs and catalytic units were found to be similar in both tissues with 10 microM Gpp(NH)p increasing activity up to 5-fold. While MnCl2 increased the response of the lung enzyme to forskolin, it reduced the response of the cardiac enzyme and uncoupled Gs from the cardiac catalytic units indicating that Gs interactions potentiate the response to forskolin. After enzyme solubilisation with n-octyl-beta-D-glucopyranoside, the response to forskolin was identical in heart and lung whether assayed with magnesium or manganese chloride, and not significantly different from the heart membrane enzyme. Overall, the results show that the relatively poor response of lung adenylate cyclase to forskolin is due to specific inhibitory interactions between the enzyme and lung membrane constituents.
Jackman
G P
GP
Alfred Hospital, Prahran, Australia.
Bobik
A
A
D000262:Adenylyl Cyclases / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002712:Chlorides; D002850:Chromatography, Gel; D005576:Colforsin / Q000494:pharmacology*; D003902:Detergents; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008168:Lung / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D008565:Membrane Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D051381:Rats
D002712:Chlorides; D003902:Detergents; C029152:G-substrate; D017895:Manganese Compounds; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015636:Magnesium Chloride; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D000262:Adenylyl Cyclases; D008274:Magnesium; C025340:manganese chloride