Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats.
Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.
De Cannière
D
D
Laboratory of Gastro-Enterological Oncology, Institut Jules Bordet, Free University of Brussels.
Ravelingien
N
N
Préat
V
V
Dehaye
J P
JP
Pector
J C
JC
D015073:2-Acetylaminofluorene; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D004052:Diethylnitrosamine; D005934:Glucagon / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D011167:Portacaval Shunt, Surgical; D051381:Rats; D011919:Rats, Inbred Strains
D006150:Guanine Nucleotides; D005576:Colforsin; D004052:Diethylnitrosamine; D005934:Glucagon; D015073:2-Acetylaminofluorene; D000262:Adenylyl Cyclases