title: Desensitization of alpha-1 adrenergic receptor-mediated vascular smooth muscle contraction.
abstract: Desensitization of alpha-1 receptor-mediated smooth muscle contraction was studied in rabbit aorta. Incubation of rabbit aorta ring segments with epinephrine (10(-6) M) for 7 hr resulted in a 10-fold loss in sensitivity of the tissue to alpha-1 adrenergic receptor-mediated contraction with no change in maximal force of contraction. This loss in sensitivity was specific for alpha-1 receptor-mediated contraction because responses to histamine and serotonin were unchanged in these aortas. Conversely, prolonged exposure of vessels to histamine (10(-5) M) led to desensitization of histamine-mediated contraction without altering responses to alpha-1 receptor stimulation. Using [125I] BE2254, a potent alpha-1 receptor antagonist, the loss in sensitivity to catecholamines was found not to be mediated by down-regulation of alpha-1 receptors nor by a loss in their affinity for epinephrine. However, desensitization was associated with a blunting of alpha-1 receptor stimulation of phosphatidylinositol turnover. These results suggest that desensitization of alpha-1 receptor-mediated contraction in rabbit aorta does not appear to be mediated by changes in receptor number or affinity but may involve alterations in receptor coupling.
authors.forename: K G
authors.initials: KG
authors.lastname: Lurie
authors.forename: G
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: B B
authors.initials: BB
authors.lastname: Hoffman
mesh_terms: D000262:Adenylyl Cyclases / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010627:Phenethylamines / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D044024:Tetralones
chemical_list: D010627:Phenethylamines; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D044024:Tetralones; C010652:BE 2254; D006632:Histamine; D000262:Adenylyl Cyclases; D004837:Epinephrine