Changes in alpha-1 and beta-2 adrenoceptor density in human hepatocellular carcinoma.
Catecholamines are involved critically in the mechanisms of liver cell proliferation by acting on hepatic alpha-1 and beta-2 adrenoceptors. To identify the role of these receptors in human hepatocellular carcinoma (HCC), the density was examined of alpha-1 and beta-2 adrenoceptors with their affinity and coupling of beta-2 adrenoceptors to adenylate cyclase in HCC tissue and in nonadjacent/nontumor tissue from the same livers. Studies were also done on healthy livers from age-matched and sex-matched patients undergoing abdominal surgery for nonhepatic diseases. Twenty-two HCC had a decrease of about 72% in alpha-1 adrenoceptor density compared with their nonadjacent/nontumor tissue and a decrease of about 40% compared with healthy controls. Nonadjacent/nontumor tissue from HCC patients had a 125% increase in alpha-1 adrenoceptor density compared with healthy livers. Twenty-three of 24 HCC had an increase of about 180% in beta adrenoceptor density compared with their nonadjacent/nontumor tissue and healthy controls. Beta adrenoceptors were coupled to adenylate cyclase, as evidenced by a guanosine triphosphate-mediated right shift in (-)-isoproterenol competition isotherms and by cyclic adenosine monophosphate (cAMP) production after stimulation with (-)-isoproterenol. The HCC tissue yielded a larger increase in cAMP than nonadjacent/nontumor tissue and healthy controls. The authors conclude that a higher density of alpha-1 adrenoceptors in nonadjacent/nontumor tissue from HCC characterizes the "healthy" part of the liver in HCC patients and that an increase in beta-2 and a decrease in alpha-1 adrenoceptor densities characterize the tumor part of the liver in human HCC.
Bevilacqua
M
M
Servizio di Endocrinologia, Ospedale L. Sacco Vialba, Milano, Italy.
Norbiato
G
G
Chebat
E
E
Baldi
G
G
Bertora
P
P
Regalia
E
E
Colella
G
G
Gennari
L
L
Vago
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases