[Functional changes of components of the adenylate cyclase complex during heterologous desensitization by...

Long-term exposure of pigeon erythrocytes to isoproterenol produces significant changes in the regulatory properties of adenylate cyclase. The enzyme sensitivity to the action of isoproterenol (0.1 mM) and GTP (0.1 mM) decreases by 50% for 15 min, that to guanylyl imidodiphosphate, a non-hydrolyseable analog of ATP, by 20-25% for 40 min. One of possible causes of the loss of the adenylate cyclase sensitivity to isoproterenol is the disturbances in the interaction between the beta-adrenoreceptor and N-protein. In experiments with restoration of the beta-adrenoreceptor and the catalytic component sensitivity to GTP, the properties of the N-protein both in the control and in desensitized preparations of plasma membranes remained unchanged. It was found that the disturbances in the beta-adrenoreceptor--N-protein interactions are due to the changes in the receptor properties. Similar results were obtained in experiments with membranes isolated from the cells to which isoproterenol or cAMP (0.1 mM) + isobutylmethylxanthine (1 mM) were added; the desensitization in this case was probably due to the phosphorylation of the beta-adrenoreceptor. A model of heterologous desensitization of pigeon erythrocyte adenylate cyclase is proposed.