Inverse regulation of calcium channels and beta-adrenergic receptors in virus-transformed human embryonal cells.
Monolayer cultures of human embryonal smooth muscle cells (HEC) were used to study the heterologous regulation of membrane beta-adrenergic receptors and Ca2+ channels. The relationships between the activation of membrane bound alpha-1 and beta-adrenergic receptors, the cyclic nucleotide response and Ca2+ channel binding were studied in a cellular model of latent virus infection (Herpes simplex, Type-2) in a human embryonal cell line. In the early stage of infection (72 h), there was a significant increase in the cell cAMP content, followed by a decrease in the binding capacity of the beta-adrenergic ligand with an increased total number of the 1,4-dihydropyridine Ca2+ channel agonist (-)-S-(3H)BAYK 8644 binding sites on the cell membrane of infected cells. The increased numbers of Ca2+ agonist binding sites were accompanied by an increased cAMP content in the cells and an increased membrane ATP-ase activity. Down-regulation of (3H)DHA binding, and an increased capacity of Ca2+ agonist binding were found after prolonged exposure of HEC to isoprenaline (10(-5) mol.l-1). Stimulation of alpha-1 adrenergic receptors with phenylephrine (10(-6) mol.l-1) was accompanied with only slight but significant increase in (3H)DHA binding and with a significant reduction in the total number of Ca2+ channel agonist binding sites.
Drímal
J
J
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Magna
D
D
Knézl
V
V
Tokárová
J
J
Drímalová
L
L
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000378:metabolism / Q000494:pharmacology; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D004622:Embryo, Mammalian; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009130:Muscle, Smooth; D010656:Phenylephrine / Q000494:pharmacology; D011863:Radioimmunoassay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D018139:Simplexvirus / Q000502:physiology; D014268:Trifluoperazine / Q000494:pharmacology
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D014268:Trifluoperazine; D004082:Dihydroalprenolol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000242:Cyclic AMP; D017301:Ca(2+) Mg(2+)-ATPase; D007545:Isoproterenol