Changes in alpha‐1 and beta‐2 adrenoceptor density in human hepatocellular carcinoma

• Published in: Cancer 1991-05, Vol.67 (10), p.2543-2551
• Main Authors: Bevilacqua, Maurizio, Norbiato, Guido, Chebat, Enrica, Baldi, Gabriella, Bertora, Pierluigi, Vago, Tarcisio, Regalia, Enrico, Colella, Giovanni, Gennari, Leandro
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Aged; Binding, Competitive; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Child, Preschool; Female; Humans; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Middle Aged; Receptors, Adrenergic, alpha - metabolism; Receptors, Adrenergic, beta - metabolism
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19910515)67:10<2543::AID-CNCR2820671026>3.0.CO;2-L

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.