Adenylate cyclase and membrane fluidity. The repressor hypothesis.
The relationships between membrane fluidity as induced by drug addition and the stimulation of adenylate cyclase by hormones (mainly catecholamines), GTP, Gpp(NH)p and NaF are reviewed. In particular, the data corresponding to pigeon erythrocyte membranes are reviewed and compared with other data published in the literature. A brief summary of the theories involved in fluidity measurements and their significance at the molecular level is also given for anisotropy of fluorescence and electron spin resonance. One of the conclusions is that the cationic drugs and neutral alcohols by perturbing preferentially the inner half-layer of the bilayer induced in pigeon erythrocyte membrane correlated multiphasic changes on fluidity and adenylate cyclase activity. This and other experimental data concerning the regulation of the adenylate cyclase are discussed in regard to a new interpretation of cyclase stimulation: the repressor hypothesis. In cell membrane the catalytic unit C is repressed by its association with a repressor complex made of the hormone receptor R and the regulatory protein N. The activation of cyclase activity is the dissociation of the catalytic unit C from the repressor complex R.N according to the equilibrium: R.N.C (inactive) in equilibrium R.N + C (active). Hormones, metal ions (magnesium), and nucleotides (GTP) are the allosteric ligands which shift this equilibrium towards the dissociation state with the liberation of the active form, membrane-bound, C unit. Gpp(NH)p, fluoride and forskolin will also shift the equilibrium toward the right. GDP and free receptors favour the associated repressed state of the system.
D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D002412:Cations; D002746:Chlorpromazine / Q000494:pharmacology; D010856:Columbidae / Q000097:blood; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000502:physiology; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D046911:Macromolecular Substances; D008560:Membrane Fluidity / Q000187:drug effects; D008954:Models, Biological; D000442:Octanols / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013045:Species Specificity; D013113:Spin Labels; D013748:Tetracaine / Q000494:pharmacology
D002210:Caprylates; D002395:Catecholamines; D002412:Cations; D003497:Cyclic N-Oxides; D005456:Fluorescent Dyes; D046911:Macromolecular Substances; D000442:Octanols; D013113:Spin Labels; D013748:Tetracaine; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D000262:Adenylyl Cyclases; C031492:octanoic acid; D002746:Chlorpromazine