title: The adenylate cyclase system in human liver: characterization, subcellular distribution and hormonal sensitivity in normal or cirrhotic adult, and in foetal liver.
abstract: 1. Adenylate cyclase (EC 4.6.1.1) activity was characterized in human liver, and its subcellular distribution compared with that of three other potential enzyme markers of the pericellular membrane: leucine aminopeptidase (EC 3.4.11.1), gamma-glutamyltransferase (EC 2.3.2.2) and 5'-nucleotidase (EC 3.1.3.5). Although these three enzyme activities were detected in each of the subcellular fractions studied, 85% of the total adenylate cyclase activity was found in the 1000 g pellet ('nuclear' fraction) with a threefold increase in specific activity as compared with the homogenate. No adenylate cyclase activity existed in the 150 000 g supernatant fraction. 2. In the 'nuclear' fraction, adenylate cyclase activity was increased in a dose-dependent fashion by glucagon with a half-maximal stimulation at 10 nmol/l and a maximal four- to seven-fold increase at 1 mumol/l. Catecholamines activated adenylate cyclase 2.5- to three-fold, with an order of potency (protokylol greater than isoprenaline greater than adrenaline greater than noradrenaline) typical of a beta 2-adrenoreceptor. Prostaglandin E1 and NaF also stimulated cyclase two- and four-fold respectively. Insulin, serotonin, dopamine, thyroid-stimulating hormone and ACTH had no effect. Adenosine provoked a weak inhibition at 0.1 mmol/l. Finally guanosine triphosphate and 5'-guanylyl imidodiphosphate induced a marked increase in basal activity, four- and eight-fold respectively, but both reduced the relative increase in enzyme activity due to glucagon or adrenaline. 3. Cyclase from foetal liver (12--16 weeks old) and cirrhotic adult liver appeared to behave similarly to that from normal liver; however, foetal cyclase was more active, and cirrhotic enzyme less active than normal adult liver. Both systems responded to catecholamines via a beta 2-adrenoreceptor. 4. These results validate the use of rat liver adenylate cyclase as a tool for pharmacological and physiological studies.
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009708:Nucleotidases / Q000378:metabolism; D012969:Sodium Fluoride / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D002395:Catecholamines; D006150:Guanine Nucleotides; D012969:Sodium Fluoride; D005934:Glucagon; D005723:gamma-Glutamyltransferase; D009708:Nucleotidases; D007931:Leucyl Aminopeptidase; D000262:Adenylyl Cyclases; D000241:Adenosine