The closely related G protein-coupled receptor kinases GRK2 and GRK3 are both expressed in cardiac myocytes. Although GRK2 has been extensively investigated in terms of regulation of cardiac beta-adrenergic receptors, the substrate specificities of the two GRK isoforms at G protein-coupled receptors (GPCR) are poorly understood. In this study, the substrate specificities of GRK2 and GRK3 at GPC...

The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by β2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative β1-adrenergic receptors, β2-adrenergic receptors were greatly enriched mouse DCT cells. In mic...

I N 1964 Oj-adrenergic receptors were first described pharmacologically using the in vitro melanocyte granule dispersion technique in Rana pipiens. The goal of these studies was to assess the intrinsic activity on o^-adrenergic receptors of methyldopa's neurotransmitter metabolites and other catecholamines. Publication of this description was delayed for 13 years, 1 until the evidence for a rec...

Protein kinases play a pivotal role in the propagation and modulation of transmembrane signaling pathways. Two major classes of receptors, G-protein-linked and tyrosine kinase receptors not only propagate signals but also are substrates for phosphorylation in response to stimulation by agonist ligands. Insulin (operating via tyrosine kinase receptors) and catecholamines (operating by G-protein-...

A procedure has been developed for purification of the porcine brain alpha 2-adrenergic receptor to homogeneity. alpha 2-Adrenergic receptors were solubilized from porcine brain particulate preparations using sequential extraction into sodium cholate- and digitonin-containing buffers. The alpha 2-adrenergic receptors in the digitonin extract were identified using the alpha 2-adrenergic selectiv...

Norepinephrine is known to inhibit its own release from presynaptic nerve terminals through alpha 2-adrenergic receptors, which presumably have a presynaptic localization. alpha 2-Adrenergic receptors (as determined by [3H]clonidine binding) appear in rat submandibular gland membranes following reserpine treatment. These alpha 2 receptors seem to be localized postsynaptically, based on the foll...

Extensive evidence demonstrates functional interactions between the adrenergic and opioid systems in a diversity of tissues and organs. While some effects are due to receptor and second messenger cross-talk, recent research has revealed an extracellular, allosteric opioid binding site on adrenergic receptors that enhances adrenergic activity and its duration. The present research addresses whet...

Catecholamine, histamine, and adenosine-mediated accumulations of radioactive cyclic AMP were assessed in adenine-labeled slices from eight rat brain regions. 2-Fluoronorepinephrine, a selective beta-adrenergic agonist, elicited an an accumulation of cyclic AMP in cerebral cortex, cerebellum, hippocampus, striatum, superior colliculi, thalamus, hypothalamus, and medulla-pons. In cerebral cortex...

Previous studies have demonstrated that glial cells in culture express several subtypes of functional adrenergic receptors. To determine if similar receptors are expressed by glia in vivo, we examined the expression of adrenergic receptors in the normal, crushed, and transected optic nerves of the rabbit and rat using quantitative receptor autoradiography. Additionally, we examined the expressi...