Desensitization of alpha-1 adrenergic receptor-mediated vascular smooth muscle contraction.

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.