The I1-imidazoline receptor and its cellular signaling pathways.
Two primary questions are addressed. First, do I1-imidazoline binding sites fulfill all the essential criteria for identification as a true receptor? Second, what are the cellular signaling pathways coupled to this novel receptor? I1-imidazoline binding sites show specificity in binding assays, linkage to physiologic functions, appropriate anatomic, and cellular and subcellular localization. Most important, binding affinities correlate with functional drug responses. I1-imidazoline binding sites meet several additional criteria identified with functional receptors: they show physiologic regulation and endogenous ligands and, most crucially, are coupled to cellular signaling events. A series of studies have identified cellular events triggered by I1-imidazoline receptor occupancy. This receptor is not coupled to conventional pathways downstream of heterotrimeric G-proteins, such as activation or inhibition of adenylyl or guanylyl cyclases, stimulation of inositol phospholipid hydrolysis, or induction of rapid calcium fluxes. The I1-imidazoline receptor is coupled to choline phospholipid hydrolysis, leading to the generation of diacylglyceride, arachidonic acid, and eicosanoids. Additional cellular responses include inhibition of Na+/H+ exchange and induction of genes for catecholamine synthetic enzymes. The signaling pathways linked to the I1-imidazoline receptor are similar to those of the interleukin family, implying that I1-receptors may belong to the family of neurocytokine receptors.
Ernsberger
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Department of Nutrition, Case Western Reserve School of Medicine, Cleveland, Ohio 44106-4906, USA. pre@po.cwru.edu
D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D054755:Imidazoline Receptors; D010743:Phospholipids / Q000378:metabolism; D011955:Receptors, Drug / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D002395:Catecholamines; D007093:Imidazoles; D054755:Imidazoline Receptors; D010743:Phospholipids; D011955:Receptors, Drug; D019204:GTP-Binding Proteins; D002118:Calcium