Somatostatin induces translocation of the beta-adrenergic receptor kinase and desensitizes somatostatin receptors in S49 lymphoma cells.
The beta-adrenergic receptor kinase is a cytosolic enzyme that specifically phosphorylates the agonist-occupied form of the beta-adrenergic receptor (beta AR). Beta AR kinase appears to be translocated from the cytosol to the plasma membrane when kin- S49 lymphoma cells are incubated with either beta-adrenergic agonists or prostaglandin E1, both of which act through receptors which stimulate adenylate cyclase. We report here that brief (approximately 20 min) exposure of wild type S49 lymphoma cells to somatostatin (which inhibits adenylate cyclase) promotes the translocation of beta AR kinase to an extent comparable to that observed in the presence of the beta agonist isoproterenol or prostaglandin E1. Beta AR kinase activity can be measured using either beta AR or rhodopsin, the retinal receptor for light, as a substrate. The translocation process triggered by somatostatin is rapid, reversible, and is associated with somatostatin receptor desensitization. The latter is apparent as an attenuation of the inhibition by somatostatin of forskolin-stimulated adenylate cyclase activity in membranes of S49 cells preincubated in the presence of the peptide. These results strongly suggest that beta AR kinase is able to phosphorylate and desensitize both stimulatory and inhibitory adenylate cyclase-coupled receptors, thus emerging as a general kinase that regulates the function of different receptors in an agonist-specific fashion.
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D017868:Cyclic AMP-Dependent Protein Kinases; D003600:Cytosol / Q000201:enzymology; D007700:Kinetics; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000378:metabolism / Q000494:pharmacology*; D051552:beta-Adrenergic Receptor Kinases
D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D013004:Somatostatin; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases